j1939

Index

a N-acetylneuraminate lyase 172, 478, 1640 a-acetolactate 991, 992 N-acetylneuraminic acid 865 a-amino acid dehydrogenases 6, 1166 N-acetylneuraminic acid aldolase (NeuA) 864 a-amino-e-caprolactam racemase 1614–1617 – natural substrates 865 a-aspartyl dipeptidase 754 – prediction, three-point binding model absorbable organic chlorides (AOX) 1824 for 869 abzyme 9A8 1743 3-acetyloctanal 934 abzymes Achromobacter obae 837, 1614 – based therapy 1737 Achromobacter xylosoxidans 1590 – mediated cell death 1753 acid–base catalysis 967 – mediated generation of peroxide 1737 acid–base chemistry 103 – in non-aqueous solutions 1770 acid phosphatases ACE inhibitors 336, 1215 – dephosphorylation by 1016, 1017 acetaldehyde 1022 ––mechanism 1018 – carboligation 923 – formation of DHAP 1020, 1021 acetaldehyde-dependent aldolases 861 – one-pot cascade reaction involving acetamidase/formamidase protein with 1024 family 613 – phosphorylation, mechanism of 1018 N-acetamidomalonate esters, alkylation 577 – structural and mechanistic acetic acid bacteria 1369 description 1013–1016 acetobacter 17 – transphosphorylation by 1017–1019 acetohydroxyacid synthase (AHAS) 920, 924 Acinetobacter calcoaceticus 1097, 1410, – from Escherichia coli, isoenzymes 926 1556, 1557 acetolactate decarboxylase 992 aconitase (Acn) 467, 476 acetolactate formation 796, 850, 927 acrylamide 522 acetonitrile, reaction medium 625 – synthesis 522 O-acetylated cis-azetidinone 287 acrylate esters 1149 acetylcholine hydrolysis by carbamates, acrylates 1149 inhibition of 1744 acrylonitrile hydration, disadvantages 523 acetylcholinesterase 1743 acyclic carboxylates, hydrolysis of 298, 299 N-acetyl-D-glucosamine 996 acyclic 1,2-diketones 936 N-acetyl-D,L-3-(4-thiazolyl)alanine 834 N-acylamino acid racemase 1630, 1631 N-acetyl-D-neuraminic acid aldolase 995 acylase process 575 acetylene hydratase 471 acylation 339 – contains tungsten atom 472 – of monohydroxy compounds 328 O-acetyl 5-hydroxyhexanenitrile 288 acyl carrier protein (ACP) 486, 487 N-acetylneuraminate (NeuNAc) acyl-CoA-derivative 62 aldolase 864–872 acyl-CoA thioesterases 765

Enzyme Catalysis in Organic Synthesis, Third Edition. Edited by Karlheinz Drauz, Harald Gröger, and Oliver May. Ó 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA. 1940j Index

N-acyl compounds 571 3a-hydroxysteroid dehydrogenase acyl donor esters 726–729 (HSDH) 1094 acyl-enzyme complex 691 a-keto acids, biocatalytic reductive amination N-acylglucosamine 2-epimerase 865, 1637, of 17 1640, 1641 a-keto acid trimethylpyruvate (2-oxo-3, 2-acyl-2-hydroxy acids 930 3-dimethylbutyric acid 1183 acyloin condensations 920–931, a-keto-b-hydroxyisovalerate 1189 1709, 1710 a-ketoglutarate 1572, 1578 – 2-acyl-2-hydroxy acids 930 – reaction mechanism 1575 – acyloin condensations 920–931 a-ketoglutarate-dependent – aliphatic acyloins 929 hydroxylases 1572 – aliphatic–aromatic acyloins 924–927 a-ketoglutarate transaminase 796 – with aliphatic donor aldehydes, and aromatic Ajinomoto Co. Inc. 31, 662, 997, 1628 acceptors 924–927 Alangium lamarckii 770 – araliphatic–aliphatic acyloins 928, 929 D-alanine amidase 602, 605 – aromatic donors, and aliphatic acceptors alanine aminotransferase 781, 1620, 1865 carboligation 927, 928 alanine dehydrogenase 800, 1167, 1187, – enzymatic acyloin condensations 1188, 1835, 1928 chemoselectivity 922, 923 DL-alanine methyl ester 600, 605 – enzymatic acyloin condensations D-alanine oligomers 595 stereoselectivity 923, 924 alanine racemase 1610, 1611 – with formaldehyde and formaldehyde alanine-scanning mutagenesis 1746 synthons 936–938 b-alanyl CoA ammonia lyase 764, 765 – with ketones and imines 935, 936 – reactions catalyzed by 765 – olefinic aliphatic and araliphatic alcohol dehydrogenases (ADHs) 6, 12, 33, 34, acyloins 929, 930 53, 61, 364, 366, 383, 386, 407, 1037, 1039, – racemic resolution via lyase/ligase 1050, 1138, 1205, 1215, 1326–1341, 1327, reactions 938–940 1407, 1592, 1888, 1928, 1935 – Stetter-type reactions 933–935 – bi-enzymatic deracemization 1389 – sugar derivatives 930, 931 – as biocatalysts 1038, 1040 – umpolung reactions, in chemistry and – commonly used 1328 biology 919–920 – glycerol dehydrogenases (GDHs) 1331–1334 acyltransferases 323, 710, 1700, 1701 – Horse liver alcohol dehydrogenase adenosine 50-triphosphate (ATP) 1006 (HLADH) 1328–1330 – enzymes used in regeneration of – Lactobacillus kefir 1334 1007–1009 – lyophilized Rhodococcus ruber expressing, adenosylcobalamin (AdoCbl). See vitamin B12 kinetic resolutions 1332, 1333 þ S-adenosylmethionine-dependent – NAD(P) regeneration systems 1335–1338 fluorinase 1578 – nicotinamide-dependent 52 S-adenosylmethionine-dependent – non-enzymatic approaches 1338–1341 halogenases 1573 – overexpressed form 1053 S-adenosylmethionine-dependent – oxidase-catalyzed kinetic resolution 1390 methyltransferases 1575, 1578, 1579 – oxidation mechanism 1327 adenylosuccinate lyase 754, 755 – oxidation of aldehydes 1408 adipodiamide 521, 522, 822 – from Rhodococcus ruber 1331 adipodinitrile 822 – screening methods to obtain novel 1049 adrenodoxin reductase (AdR) 1256, 1257 – short-chain zinc-independent 1407 Agrobacterium radiobacter 150, 370, 373, 388, – sources, useful for biocatalysis 1042–1049 399, 1126, 1129 – substrates and kinetic constants for 1411, Agrobacterium tumefaciens 433, 660, 1178, 1412 1179, 1388, 1641 – substrate spectra of 1328 Agrocybe aegerita 1233, 1555, 1559 – Sulfolobus solfataricus 1330 a-hydroxy acid dehydrogenases 6 – Thermoanaerobacter brockii (TBADH) 1330 11a-hydroxylation of progesterone 1257 – from thermophilic organisms 1330, 1331 Index j1941

– types of 1040–1042 aldose synthesis, inverted approach for 886 – yeast alcohol dehydrogenase (YADH) 1330 aldos-2-ulose dehydratase (AUDH) 485, 486 alcohol oxidases 1346 alginate biosynthesis 594 – common oxidases 1347–1354 aliphatic a/b-unsaturated acceptor 929 – methods to diminish/avoid hydrogen aliphatic acyloins 929 peroxide 1345–1347 aliphatic alcohol oxidases 1347 alcohols, oxidation of 1325, 1408. See also aliphatic–aromatic acyloins 924–927 alcohol dehydrogenases; alcohol oxidases aliphatic donor aldehydes 925 alcoholysis of 3-arylglutaric anhydrides 339 aliphatic olefins, dihydroxylation of 1303 alcoholysis of dibenzoates 338 alkaline phosphatases 1009 aldehyde dehydrogenases 1410 – application in dephosphorylation 1012 – for biocatalytic applications 1410 – structural and mechanistic aldehyde lyases, syntheses using 993–995 description 1010, 1011 aldehyde oxidations 1392, 1407, 1409, – transphosphorylation by 1012, 1013 1414, 1416 alkaloids 770 – alcohol dehydrogenases (ADHs) 1407, alkane monooxygenases 1236, 1279, 1280, 1408 1287 – aldehyde dehydrogenases 1408–1410 alkanes 1248 – enzyme classes/applications 1392–1407 alkenal/one oxidoreductases (AORs) 1138 – with intact microbial cells 1414–1418 alkene, chemoenzymatic epoxidation of 1290 – monooxygenases 1410–1414 alkene monooxygenase 366, 1235, 1278, – oxidases 1414 1280, 1282, 1497, 1498 aldehyde reduction 1049, 1098–1101 alkene reductases, applications of 1143 – general process concept 1050 – acrylates and acrylate esters 1149 aldehydes/acids from primary alcohols – a,b-unsaturated aldehydes and – stopping oxidation at aldehyde stage ketones 1143, 1147, 1149 1363–1369 – nitroalkenes 1149, 1150 – through oxidations 1369–1373 – reductions of 2-cyclohexenones by alditol oxidase (AldO), substrate range Saccharomyces pastorianus OYE 1147 of 1355, 1356 – stereochemical investigations of old yellow aldo-keto reductases (AKRs) 1040 enzymes 1146, 1147 aldol adduct, formation of 1025 alkene reduction by whole microbial – stereo-diversity, generation 858 cells 1111, 1112 aldolases 1193 – Bakers’ Yeast 1112–1114 – based process 862 – microbial species 1114, 1115 – catalysis 858 alkene reductions, by isolated enzymes 1116 – catalyzed asymmetric synthesis 882 – bacterial old yellow enzyme superfamily – classes 858–861 members 1124, 1129 – class I/II aldolases, schematic – bacterial OYE homologs 1125–1128 mechanism 860 – enoate reductases 1135–1138 – nucleophilic donor substrates 859 – fungal old yellow enzyme superfamily – one-pot cascade reaction involving members 1121, 1124 with 1024 – fungal OYE homologs 1122, 1123 – reaction 866 – medium-chain dehydrogenases aldol condensation of enolate 1740 1138–1142 aldol reactions 857–909 – plant old yellow enzyme superfamily – aldolases classes 858–861 members 1129, 1130, 1135 – 2-deoxyribose 5-phosphate aldolase – plant OYE homologs 1131–1134 861–864 – Saccharomyces pastorianus old yellow – DHA/DHAP-utilizing aldolases 877–901 enzyme 1116–1121 – glycine-utilizing aldolases 901–908 – short-chain dehydrogenases 1143, 1144 – pyruvate/phosphoenolpyruvate-utilizing a-alkylated phenylserine derivatives aldolases 864–877 synthesis 908 aldose reductase 1392 2-alkyl cyclohexanones 1477 1942j Index

alkyne oxyfunctionalization, type of 1314 – synthesis 661, 664 allenols 313 L-amino acid amidases 605 DL-a-allylalanine amide 608 – crystal structures 601 allyl Grignard reagents 975 amino acid amides 592 allylic alcohols 320 – dynamic kinetic resolution of 1615 allysine ethylene acetal 1192 amino acid amides, enantioselective Almac Sciences, enzyme production hydrolysis 574–618 – carbonyl reductase 1850, 1851 – enantiopure b-amino acids by – contact information 1850 b-aminopeptidases synthesis 613–618 – hydrolases 1852–1854 – enantiopure a,a-disubstituted amino acids – nitrile hydratases and nitrilases 1851 synthesis 607–613 Alzheimer’s disease 314 – enantiopure a-H-a-amino acids Amano Enzyme Company, enzyme synthesis 575–607 production 1854 a/b-amino acid amides, hydrolysis 568 – acylases 1857 amino acid dehydrogenase (AADH) 795, – contact information 1855 799, 800 – lipases 1855, 1856 amino acid exchange per enzyme – proteases 1857 molecule 141 amidase catalyzed hydrolysis 567 amino acid oxidase (AAO) 53, 789, 791, 1197, amidases 1538, 1539 – antibodies 1758, 1759 amino acid racemase 587, 796, 1611, 1614, – basic reaction catalyzed 562 1617, 1671 – catalyzed reactions 580 D-amino acids 623 –– disadvantage 628 – specific enzymes 606 – inhibitors, usage 540 – synthesis 594 – overview 564–566 aminoacylase 219 – process 577 aminoacyl-tRNAs 735, 739 – resolution process 577 amino amidase 219 amidase signature (AS) family 562, 580, 603 L-amino amidase 580 amidase transfer reaction, with p-aminobenzoic acid 1562 hydroxylamine 563 p-aminobenzyl amine 1562 amide hydrolyzing enzymes, properties 4-aminobutyrate 796 of 561 3-aminobutyrate or 3-aminoisobutyrate 765 amides hydrolysis 561–629, 1815 a-amino-e-caprolactam (ACL) 577, 578 – amino acid amides, enantioselective DL-a-amino-e-caprolactam (DL-ACL) 570 hydrolysis 574–618 7-aminocephalosporanic acid (7-ACA) 826, – azido acid amides, enantioselective 1537, 1587 hydrolysis 620–622 aminocyclitol analogues 888 – carboxylic acid amides, enantioselective 7-aminodeacetoxycephalosporanic acid hydrolysis 561–569 (7-ADCA) 827 – C-terminal amide bond, selective 2-amino-D2-thiazoline-4-carboxylate cleavage 622–628 racemase 1628 – cyclic amides, enantioselective amino functionalities 10 hydrolysis 570–574 6-aminopenicillanic (6-APA) acid 21, 826 – and formation 549, 1758 aminopeptidase 586 – hydroxy acid amides, enantioselective D-aminopeptidase (DAP) 595, 600, 601 hydrolysis 618–620 2-aminophenol 1505 amidohydrolases 826 (S)-2-amino-4-phenylbutanoate 1191 amine acceptor (pyruvate) 1538 p-aminophenylic acid 1562 amines/amino acids in whole-cell/ p-aminophenylsulfonic acid 1562 threeenzyme system aminotransferases 781, 782 – catalytic cycle for the production 1220 – advantages, use of 789 L-amino acid – subdivision, based on sequence/structural – enzymatic racemization 586 similarity 783 Index j1943 ammonia lyases 749 – properties 758, 759 ammonium sulfate 213 – structure 759, 760 ampicillin synthesis 831 – substituted cinnamic acids conversion a-amylase 516, 517, 1921 into 763 Anabaena variabilis 762 aromatic compounds, biotransformations of ANHase 534 – catechols 1515 1,5-anhydro-D-fructose dehydratase – cis-dihydrodiols in synthesis 1511–1515 (AFDH) 485, 486 – dihydroxylation 1508 animal enzymes 196 – future challenges 1519–1520 – extraction of 198 – monohydroxylations 1515, 1516 anion exchange chromatography 581 – reaction selectivity 1509 anionic emulsifiers 1842 – regioselectivity 1509, 1510 anion, nucleophilic attack of 1441 – ring-cleavage reactions, products 1517, antibody 4C6 1740 1518 antibody catalysis, applications of 1737, – ring heteroatoms, effect of 1511 1767–1770 – side chain oxidation 1517 antibody, catalyzing photocyclization of 1741 – stereoselectivity 1510 antibody esterases. See esterase antibodies – substrate specificity 1508, 1509 anti-DNA antibodies in autoimmune – whole cell vs. cell-free reactions 1506–1508 pathologies 1751 aromatic dioxygenases 1557 antigen-directed abzyme prodrug aromatic donors, and aliphatic acceptors therapy 1763–1765 carboligation 927, 928 – ADAPT approach 1764 aromatic hydrocarbon oxidation, antinuclear-DNA autoantibodies 1752 enzymology of 1487 antipodal lactones, microbial – aromatic compounds, oxygenation 1471 metabolism of 1487–1490 anti-ribonucleoprotein (RNP) – dioxygenases 1490–1496 antibodies 1751 – extradiol dioxygenase 1503–1506 anti-TSA antibody catalysts 1735 – intradiol dioxygenase 1500–1503 antiviral agent 1003 – monooxygenases (Di-iron) 1496–1498 apoenzyme 541 – monooxygenases (flavoprotein) apoptosis 1751, 1752 1498, 1499 apparent catalytic promiscuity 1716 – ring cleavage dioxygenases 1500 a 1-proteinase inhibitor 691 aromatic hydrocarbons 1497 aqueous–organic two-phase systems 925 aromatic monohydroxylation 1515, 1516 Arabidopsis thaliana 1142, aromatic oxidations. See aromatic compounds, 1273, 1310 biotransformations of; aromatic araliphatic–aliphatic acyloins 928, 929 hydrocarbon oxidation, enzymology of arene cis-dihydrodiols, reaction options aromatic ring hydroxylating for 1513 dioxygenases 1491, 1496 arginine, CGA coding for 123 Arthrobacter keyseri 1495 argininosuccinate lyase 755 artificial biocatalysis in vivo, Arg-specific peptidases 720 generation of 1769 aromatic aldehydes, direct artificial proteolytic abzymes, hydroxymethylation 938 induction of 1763–1765 aromatic/aliphatic aldehydes, arylacetonitrilases 550 transhydrocyanation 964 aryl-alkyl amines 802 aromatic amino acid ammonia lyases 758 L-5-arylalkylhydantoinases 658 – applications 761–763 arylamines 1561 – biocatalytic relevance 761–763 arylnitro compounds 1561 – distribution 760, 761 3-aryloxy-1-nitrooxypropan-2-ols 314 – diversity 760, 761 aryloxynitropropanols 316 – engineering studies 763, 764 (S)-2-arylpropanols 1100, 1101 – mechanism 759, 760 2-arylpropionic acids 335 1944j Index

Asahi Kasei Pharma Corporation, enzyme – structural resemblance 888 production azidoacetyl 872 – contact information 1860 azido acid amides, enantioselective – dehydrogenases 1863, 1864 hydrolysis 620–622 – hydrolases 1861, 1862 b-azidoalcohols 61 – lyases, decarboxylases, ligases and 1865 a-azido carboxylic acids 620 – oxidases 1862, 1863 6-azido-6-deoxyfructose 883 – oxynitrilases 1860 2-azido-2,4-dimethylpentanamide 621 ASA Spezialenzyme GmbH, enzyme 3-azidoglyceraldehyde 889 production 1857 L-2-azidohexanoic acid 621 – contact information 1858 2-azidohexanoic acid amide 620 – hydrolases 1858, 1859 (RS)-3-azido-2-hydroxypropanal 1024 – oxidoreductases 1859 2-azido-2-methyl-3-phenylpropanamide 621 – oxynitrilases 1860 2-azidophenylacetic acid amide 620 Ascophyllum nodosum 1559 3-azido-2(R)-hydroxypropanal 883 aspartases 750 2,20-azino-bis(3-ethylbenzothiazoline-6- aspartate b-decarboxylase 992, 993 sulfonic acid) (ABTS) 1344, 1361 aspartate racemase 1618, 1624, 1625 azlactones 301 aspartate residue, catalytic role 563 aspartic peptidases 680, 683, 687, 689 b Aspergillus fumigatus 1254, 1256, 1721 Bacillus amyloliquefaciens 120 Aspergillus japonicus 1363 Bacillus cereus 1187, 1219 Aspergillus niger 398, 399, 400, 401, 1286, Bacillus licheniformis 714 1306 Bacillus megaterium 130, 791, 850, 1817 Aspergillus oryzae 835 Bacillus proteolicus 844 assembly of designed oligonucleotides Bacillus sphaericus 1179, 1189, 1193, 1546 (ADO) Bacillus stearothermophilus 796, 1184, 1257 – general concept of 139 Bacillus subtilis 78, 123, 289, 327, 796, asymmetric functionalization reaction 858 1210, 1294 asymmetric HCN addition, to aldehydes and Bacillus thuringiensis 1243 ketones 994 bacterial host, advantage of 121 atorvastatin 1602 bacterial P450 monooxygenase 93 ATPase 690 Baeyer–Villiger bio-oxygenations 1455, 1475 ATP-dependent enzymatic reactions 1419 – in natural product synthesis, ATP-dependent peptidases 689 regiodivergent 1473, 1474 aureothin 1561 Baeyer–Villiger biotransformation 1444 AurF-catalyzed reaction 1561 Baeyer-Villiger monooxygenases (BVMOs) 7, autoantibodies 1747 168, 1554, 1556 autocatalytic splicing process 602 – Baeyer–Villiger reaction to heteroatom autoxidation 1232 oxygenation 1452 Avicel cellulose 979 – bio-oxidation of poly-ketone a-vinyl amino acids 311 substrates 1468 ()-6-azabicyclo[3.2.0]heptane-7-one – biotransformations 1447 – bio-resolution 573 – catalyze regio- and enantioselective rac-2-azabicyclo[2.2.1]hept-5-en-3-one oxidations 1462 (c-lactam) – certain sub-clusters of 1451 – resolution reaction 571 – chemoselectivity of 1471 6-azabicyclo[3.2.0]hept-3-en-7-one – divergent oxygenations of fused – Rhodococcus equi catalyzed kinetic cyclobutanones 1465 resolution 573 – dynamic kinetic resolution 1462 azasugar phosphonic acids, bifunctional – enantiocomplementary access 1470 class 891 – enantiocomplementary lactones, synthetic azasugars exploitation of 1471 – precursors, utilization 862 – exploitation of 1469 Index j1945

– functional group selectivity of 1453 benzaldehydes – heterocyclic lactones, synthetic exploitation – carboligation 923 of 1472 – regiocomplementary chemical and biological – 1-indanones, regiocomplementary oxygenation of 1463 oxygenation of 1463 benzene dioxygenase (BDO) 1508 – kinetic resolutions 1473 – 2,3-specific enzymes 1510 – monocyclic substrates for 1454 benzoate – mutation studies on 1476 – dioxygenation of 1422 – oxidizable heteroatom 1452 – family 1493 – oxygenation pathways 1452, 1468 – sequential oxidation of 1422 – phylogenetic relationships 1451 benzo-fused cyclic alkenes, conversion – polycyclic substrates for 1456 of 1304 – recombinant and typical substrate benzoic acid 1422 types 1450 – oxidations of 1419 – self-sufficient fusion protein biocatalysts, benzoic acid dioxygenase (BZDO) 1508 concept of 1444, 1445 benzoin condensations 931–933 Baeyer–Villiger oxidations 7, 103, 1233, 1439, – cross benzoin condensations 932, 933 1463, 1468 – umpolung reactions in chemistry and – BVMOs, mechanistic cycle for 1440–1443 biology 919, 920 – catalysts 1290 benzoylformate decarboxylase (BFD) – cofactor recycling 1443–1448 922, 928 – enzyme engineering 1474–1477 – physiological function 931 – enzyme structure 1440–1443 – (S)-selectivity 928 – of functionalized racemic 1472 – stereoselective acyloin-like reactions 173 – within pentalenolactone biosynthesis – structure-based engineering 928 1449 – thiamine diphosphate-dependent 173 – of premithramycin B by MtmOIV 1448 benzyl alcohol 1497 – regiodivergent 1472 2-(6-benzyloxy-4-methyl-4-hexenyl)propane-1, – synthetic applications 3-diol 341 ––bioactive compound, application 6-benzyloxy-(3R,5S)-dihydroxyhexanoic acid 1469–1474 ethyl ester 1218 ––chemoselectivity 1452, 1453 biased mutation-assembly (BMA) 137 ––desymmetrization reactions 1453–1456 bicyclic pyrrolidine ––enzyme platform 1448–1452 – symmetrical, conversion ofconversion ––kinetic resolutions 1456–1462 of 1545 ––natural product synthesis 1469–1474 1,10-binaphthyl-2,20-diols (BINOL) 333 ––regioselectivity 1462–1469 binuclear non-heme iron enzymes 1270 barbiturase, gene organization 669 biocatalysis 1807 basic local alignment search tool (BLAST) 91 – advantage of 16 batch fermentation 1592 – asymmetric oxidations, with oxygen 1586 batch stirred tank reactor (BSTR) 220, – concepts 43–63 222, 224 – deracemization reactions 1391 – Michaelis–Menten kinetics 221 ––selection of 1393–1404 – reactor selection criteria 223 – production, of insulin 841 Bayer–Villiger oxidations 1276 – production processes 32, 561 BBI Enzymes 1865 – racemizations 1386–1388 – contact information 1866 – reactor scale-up 240 – miscellaneous hydrolytic and redox – for reductive amination 16 enzymes 1867 biocatalysts 191, 195, 218, 697 Beauveria bassiana 398, 404, 1256, 1590 – advantage of 14 Beauveria brongniartii 1815 – alcohol dehydrogenases 1038, 1040 Beauveria sulfurescens 398, 1297 – application 540 b-elimination 1756 – commercial 214 benzaldehyde lyase (BAL) 922, 927 – downstream processing 230 1946j Index

– recovery 230 – biomass for 15 – for sulfoxidation 1554 – development of 22 Biocatalysts Ltd., enzyme production 1870 – enzyme suppliers for 194, 195 – carbohydrate hydrolases 1871 – enzymes used in, regulatory – contact information 1871 assessments 194 – lipases and esterases 1872 – in organic synthesis 14 – proteases and peptidases 1872, 1873 BioZyme 1865. See BBI Enzymes biocatalytic ketone reduction 1049 biphenyl dioxygenase (BPDO) 1495, 1508 – enzyme-coupled cofactor- 1,5-bis(4-allyldimethylaminophenyl)-pentane- regeneration 1050, 1051, 1053 3-one 1743 – general process concept 1050 bis(tert-butyldimethylsilyl)ether 1511 – in situ cofactor-regeneration 1050 (R,S)-[3,5-bis(trifluoromethyl)phenyl]ethan-1-ol – substrate-coupled cofactor-regeneration – chemoenzymatic dynamic kinetic resolution concept 1050 of 1839 – use of excess isopropanol 1051 blood factors, as targets for induced catalytic biocatalytic kinetic resolutions antibody response 1761 – overview of 1380–1384 Boc-glycyl derivative conversion 868 biocatalytic nitroaldol (Henry) reaction 969 Boilysin 1875, 1892 biocatalytic oxidation boron-containing alcohols 321 – of primary alcohol 1367, 1368 Botryosphaeria dothidea 1308 biocatalytic processes, types of 45 bovine pancreatic trypsin inhibitor (BPTI), – cascade/domino processes 60, 61 polarizable model of 97 – diastereomers 58–60 a-branched D-amino acid 907 – kinetic resolutions (KRs) branched-chain aminotransferase –– yield limitation of 50–58 (BCAT) 812 – novel concepts 61–63 branched-chain keto acid decarboxylase – parallel kinetic resolutions (PKRs) 48–50 (KdcA) 925 biocatalytic triple-bond Braunschweig Enzyme Database oxyfunctionalization 1315 (BRENDA) 68 biocatalyzed-cascade processes 61 Brevibacterium flavum 846 BiocatCollection, enzyme production Brevibacterium imperiale 1817 – contact information 1869 (þ)-exo-brevicomin 893 – enzyme availability 1870 2-(bromoniethyl)naphthalene (BrNP) 1813 biocompatible/hemocompatible bromoperoxidase 1559 materials 1812 b-substituted a-amino acids, stereoinversion bioconversion process 865 of 1541 bioethanol 1656, 1657 b-substituted cycloketones 1466 biofuels 218 – bio-oxidation of 1467 biological phosphorylating agents 1004 Bucherer–Bergs reaction 840 bio-oxygenation 1308 Bucherer method 651 biopolymers, surface functionalization 1819 Burkholderia cepacia 1418 bioprocess engineering strategy 239, 241 – oxidation of aldehydes 1418 bioreactors 1248 Burkholderia cepacia lipase 135 Bio-research products, enzyme production Burkholderia plantarii 839 – contact information 1868 Burkholderia xenovorans 767 – miscellaneous enzymes 1868 O-butanoyl (S)-monastrol 290 Bio-Research Products, Inc. (BRP) 1868 4-(tert-butoxycarbonyl)piperazine-2- bio-resolution process carboxamide, kinetic resolution 581 – development 571 N-butyldeoxynojirimycin biosynthesis pathway 935 – inhibitor for 1594 biotinylated phosphonate 1746 – synthesis of key intermediate for 1594 biotransformations 14, 191, 823, 825, 845, tert-butyl hydroperoxide (tBHP) 1357 850, 851 tert-butyl 4-hydroxypentanoate 319 – AMFEP guidelines 194 tert-butylisonitrile (tBuNC) 536 Index j1947 butyric acid 519 ––cysteine decarboxylase 1707 BV04-01 abzyme 1750 ––decarboxylases 1704, 1705 BV04-01 mutants, kinetic parameters of 1750 ––pyridoxal-dependent enzymes 1705–1707 ––serine hydrolases 1703, 1704 c – Michael additions and 1707 Cahn–Ingold–Prelog (CIP) priority 50 ––pyridoxal enzymes 1708, 1709 – enantiotopic groups, nomenclature of 51 ––serine hydrolases 1707, 1708 C4a-(hydro)peroxyflavin intermediate 1498 – stereochemistry 859 Caldariomyces fumago 1233, 1287, 1553, carbon–carbon lyases 991 1558, 1560 carbon nucleophiles, use of 9 camphor carbon–oxygen lyases 514 – bio-oxidative degradation of 1467 carboxamide 606, 622 Campylobacter jejuni 448, 769 carboxyfluorescein 402 Candida antarctica 154, 1811, 1839, 1842 carboxy-group-containing cosubstrate 1290 Candida antarctica lipase B (CALB) 140, 1843 carboxylates Candida antartica lipase (CAL) 100, 105, 1300 – with chiral acid moiety, resolutions based – enantioselectivity of 101 on 265 Candida boidinii 1184, 1192, 1214, 1215, ––amino-functionalized stereogenic center at 1218, 1219 a-position 270–273 Candida lipolytica 1279 ––amino-functionalized stereogenic center at cantaxanthin 1254 b-position 276–280 caprolactone 1818 ––axial and planar chirality 283, 284 captopril (1-[(2S)-3-mercapto-2- ––hydroxy-(or oxo-)functionalized stereogenic methylpropionyl]-l-proline) 336 center at a-position 273–275 carbamate–abzyme inhibition 1743 ––hydroxy-(or oxo-)functionalized stereogenic carbamates 567 center at b-position 280, 281 N-carbamoyl-a-amino acid, ––non-functionalized stereogenic center at D-enantiomer 658 a-position 266–270 D-N-carbamoylase 658, 659 ––remote stereogenic center 282, 283 – crystal structure 664 ––stereogenic heteroatom center at – problems 659 b-Position 282 L-N-carbamoylase 659 ––two heteroatom-substituted stereogenic N-carbamoyl-L-aspartic acid, non-enzymatic centers at a,b-positions 275, 276 cyclization 658 – with chiral alcohol moiety, overview of N-carbamoyl D-p-hydroxyphenylglycine 21 resolutions of esters 284, 285 – microbial production of 21 ––with axial chirality at the alcohol carbaryl hydrolases 567 moiety 291 carbohydrate-active enzymes 1900 ––with chiral alcohol moiety 285, 286 Carbohydrate-Active EnZymes (CAZY) ––with heteroatom functionalized chiral database 70 alcohol moiety 286–289 carbohydrate-degrading enzymes 1004 ––with remote stereogenic center at alcohol carbohydrate epimerases 1641 moiety 289–291 – ketohexose 3-epimerases 1641, 1643 carboxylates via esterification, enantioselective – sugar nucleotides produced by 1642 formation of 302 carbohydrates 417 – enzymatic resolution of carboligation reactions 922 ––primary alcohols 304–314 carboncarbon bond 920 ––rac-diols 327–334 – cleavage reaction 932 ––secondary alcohols 314–326 carboncarbon bond formation 857, 860, ––tertiary alcohols 327 1703 – enzymatic resolution of rac-acids and rac- – acyloin condensation 1709, 1710 esters – cationic polyene cyclizations by terpene ––with stereocenter at a position 334–336 cyclases 1710–1712 ––with stereocenter at b position 337 – enolate formation for aldol addition 1703 – resolution of rac-alcohols 302, 303 1948j Index

carboxylic acid amides, enantioselective CC bonds hydrolysis 561–569 – formation 857, 860, 1703 carboxylic acids oxidation 1418 – cleavage 932 – formate dehydrogenase 1420, 1421 C¼C bonds 467–469 – with intact microbial cells – acetylene hydratase 471 –– benzaldehyde, production of 1421, 1422 – aconitase (Acn) 476 –– cis,cis-muconic acid, microbial production – aldos-2-ulose dehydratasee 485, 486 of 1422 – carotenoid hydratases 469, 470 –– substituted benzoates, biotransformation – citraconase 475, 476 of 1422, 1423 – dehydroquinase 484 – pyruvate oxidase 1418–1420 – dihydroxy acid dehydratase 477, 478 carboxylic ester hydrolases reactions 504 – diol dehydratase/glycerol dehydratase carboxypeptidases 708 472, 473 carboxypeptidase Y (CPD-Y) 624, 708, 730 – fatty acid biosynthesis 486–489 carnitine 521 – fatty acid degradation, b-oxidation 489–491 b,b-Carotene cleavage 1310 – fumarase 473–475 – products formed 1312 – hydratase-tautomerase bifunctionality 483 carotenoid cleavage oxygenases – hydroxycinnamoyl-CoA hydratase lyase – substrates 1311 (HCHL) 491, 492 – typical products 1312 – 2-hydroxy-4-dienoate hydratases 478–482 carotenoid hydratases 469, 470 – kievitone hydratase 471 carotenoid oxygenases 1273 – malease 475, 476 carotenoids 1254 – oleate hydratase 469 k-carrageenan gel 518 – scytalone dehydratase 484, 485 cascade/domino processes 60, 61 – serine dehydratases 482 cascade reactions, in one pot using – sugar dehydratases 478 phosphorylated intermediates – threonine dehydratases 482 1022–1026 – urocanase 476, 477 catalytic activity of the lipase B (CALB) 140 – water addition to conjugated double catalytically promiscuous enzyme activities bonds 473–492 – industrial processes 1837 – water addition to isolated double catalytic antibodies 1735 bonds 469–473 – abzyme-mediated chemical C¼C double bonds, dihydroxylation 1302 transformations 1736 – aliphatic olefins/conjugated alkenes – and hormonal dysfunctions 1760, 1761 1303–1305 – and neurodegeneration 1762, 1763 – terpenes 1305–1308 – procedure, to obtain 1736 C¼C double bonds epoxidation 1288 catalytic asymmetric cross-benzoin – aliphatic olefins 1278–1290 condensation 933 – CYP450 reaction cycle 1276 catalytic enzyme promiscuity 103, 1369, 1837 – terpenes 1295–1302 – in single enzyme 1697–1699 – vinylaromatic substrates 1290–1295 catalytic reaction 664 CC multiple bond catalytic turnover 1507 oxyfunctionalization 1269 catalytic vaccines 1737 – double bonds, oxidative cleavage of catalyzing isomerization reactions 1308–1313 – enzymes capable of 10 – enzymes capable of 1269, 1270 catechol 1,2-dioxygenase (C12DO) 1500 –– binuclear non-heme iron catechol 2,3-dioxygenase (C23DO) 1503 oxygenases 1270 catecholic compounds, ring cleavage of 1500 –– flavin-dependent oxygenases catechol, ring-opening biotransformations functionalize 1276, 1277 of 1518 –– heme-containing monooxygenases Caulobacter crescentus 405 1274–1276 N-Cbz-protected prolinal 891 –– mononuclear non-heme iron C6–C12 alk-1-enes 1282 oxygenases 1270–1274 Index j1949

––peroxidases 1277, 1278 chemoselectivity 43 – triple bond oxyfunctionalization – principles 922 1313–1315 Chen equations 47 C:C triple bond chiral alcohols 1212 – functionalization of 1314 chiral auxiliary-mediated processes 857 – P450 monooxygenases 1314 chiral compounds CDP-3,6-dideoxy-4-keto-D-glucose – formation of 163 – carbonyl function 935 – in vitro synthesis 857 cell-free biocatalytic system 1373 chiral epothilone A cell-free protein synthesis 1420 – chemoenzymatic synthesis 862 cell metabolic pathways 61 chiral intermediates, catalytic synthesis cellobiose dehydrogenase (CDH) of 160 1342, 1352 chirality 1808 – Artificial regeneration systems 1352 chiral Lewis acids 857 Cellulomonas fimi endo-b-1,4-xylanase chiral secondary alcohols, oxidation of 1379 1820 chiral tertiary alcohols 260 cellulose ChiralVision BV, enzyme production 1873 – in vitro enzymatic synthesis of 1807 – contact information 1873, 1874 cephalosporin C 1537 – extremely thermostable proteases 1875, – esterase-catalyzed hydrolysis of 157 1876 Cetus process 1373, 1378 – genencor proteases 1874, 1875 CH-acidic aldehydes 928 – generic Candida antarctica Lipase B C–H-acidic functionality 36 (CaLB) 1874 Chaetomium globosum 1253 – immobilization support material chelating agents 680 ––ImmobeadÔ 1876 chemical transformations, abzyme- Chlorella sorokiniana (vulgaris) 1557, 1559 mediated 1737 chlorinase 1578, 1579 chemocatalysis chlorination 1572 – advantage of 16 – of peptidyl carrier protein-tethered – multistep chemical 16 substrate 1578 chemocatalysts 13 chlorobenzene dioxygenase (CBDO) 1508 chemoenzymatic asymmetric chloroethanal 863 hydrogenation 1541 6-chlorohydroxyquinol 1499 chemoenzymatic conversions 219 (R)-o-chloro-mandelonitrile 953 chemoenzymatic deracemization p-chloromercuribenzoic acid (pCMB) method 1542 595 chemoenzymatic industrial processes chloroperoxidase 1295, 1553, 1557, 1558 1838 – catalyzed oxyfunctionalizations 1297 – amines/amino acids, chemoenzymatic – epoxidation of 1296, 1297 deracemization of 1839, 1840 chloroperoxidase from Caldariomyces fumago – chemoenzymatic dynamic kinetic resolution (CPO) 1278, 1303, 1356 (DKR) – epoxidation, and heteroatom ––of secondary alcohols 1838, 1839 oxyfunctionalization reactions 1357 – xolvone, chemoenzymatic synthesis – oxidation mechanism of 1357 – of 1840, 1841 in situ H2O2 generation methods 1358 chemoenzymatic multistep drugs chlorophenol 4-monooxygenase 1499 synthesis 37 2-chloropropionic acid 387 chemoenzymatic platform processes, for 5-chloropyrazine-2-carboxylic acid esters deracemization 1839 825 chemoenzymatic production methods, (3R,5R)-6-chloro-2,4,6-trideoxyhexose 863 competitiveness 577 cholesterol oxidase (ChOx) 1354 chemoenzymatic syntheses – oxidation of cholesterin 1354 977 chorismate mutase 1661–1663, 1739 – of RNase A 735 Chromobacterium violaceum 1236 1950j Index

chymotrypsin 704 – laccase 1548 – catalyzed peptide synthesis using – L-amino acid oxidase 1535, 1536 4-guanidinophenyl esters 725 – 2-methylindole, treatment of 1550 – catalyzed (8 þ 16) segment synthesis – peroxidase 1548 of the Ht 31 736 – P450 monooxygenase 1547, 1548 a-chymotrypsin 296 – racemic amino acids, deracemization cis-b-methylstyrene 1717 of 1539–1542 cis,cis-muconic acid – tyrosinase 1548, 1549 – microbial production of 1422 C–N lyases 749 cis-1,2-diarylcyclobutanol 1741 – processes using 845–848 cis-dihydrodiol sulfoxides 1557 coating lipase 1811 cis-2,3-epoxyheptene 404 cobalamin 771 cis-2-heptene epoxidation 1288 CO bonds cis–trans isomerases 1609, 1643–1646 – industrial application and processes – linoleate cis–trans isomerase 1644, 1645 forming 503–525 –– substrates for 1645 – processes using glycosidases 513 – maleate cis–trans isomerase 1643, 1644 – processes using glycosyltransferases – monounsaturated fatty acid cis–trans 514–517 isomerases 1646 – processes using lipases 503–513 citalopram 314 – syntheses using carbon–oxygen (S)-(þ)-citalopram 315 lyases 517–523 citraconase 475, 476 Codexis, Inc, enzyme production – enantioselectivity 475 1877 – stability 475 – catalog enzyme products 1878–1880 citric acid cycle 476 – cofactor recycling enzymes 1880 Citrobacter amalonaticus 757 – contact information 1878 Citrobacter freundii 1023 – other enzymes 1881 Claisen rearrangement reaction 1739, 1740 cofactor-independent amino acid Claisen-type condensation 487 racemases 1618 c-LEcta GmbH, enzyme production 1876 – reaction mechanism 1619 – contact information 1877 cofactors – lipases 1877 – enzymatic syntheses 13 cloning vectors 694 – regeneration processes of 12, 13 Clostridium acidiurici 1239 Colletotrichum nicotianae 1295 Clostridium butyricum 1137 column chromatography 978 Clostridium propionicum 764, 769 Comamonas testosterone 1497 Clostridium purinolyticum 1239 combinatorial active site saturation testing Clostridium sporogenes 1150 (CASTing) 134, 401, 1475 Clostridium tetani 768 combinatorial consensus mutagenesis Clostridium tetanomorphum 756, 757 (CCM) 135 Clostridium thermoaceticum 1137 combinatorial multiple-cassette mutagenesis Clostridium tyrobutyricum 1135 (CMCM) process 146 clostripain-catalyzed acyl-transfer 704 commercial enzymes 191 CMP-sialate synthase (CSS) 870 complementarity determining regions CN acting enzymes on industrial scale (CDR) 1735 821, 822 complete active site saturation test CN bonds, oxidation of 1535 (CAST) 1475 – amine oxidases complex multi-substrate reactions –– monoamine oxidase MAO-N 1542–1545 909 – amino acid dehydrogenases 1545–1547 computer-assisted secondary structure – D-amino acid oxidase 1537–1539 prediction 602 – enzyme-catalyzed 1535 continuous plug flow reactor (CPFR) – flavin-dependent monooxygenase 220, 222 1547, 1548 – reactor selection criteria 223 Index j1951 continuous stirred tank reactor (CSTR) 220, – HNL-catalyzed biotransformations, 222, 224 experimental techniques 977–981 – Michaelis–Menten kinetics 221 – (R)-HNL for synthesis 949 – reactor selection criteria 223 – HNLs improvement by enzyme engineering, copper-containing amine oxidases 1544 enzyme stabilization 970–972 copper-containing onoamine oxidases, – hydroxynitrile lyase catalyzed addition of enantioselective 1545 HCN to aldehydes 953–955 copper-containing tyrosinases 1516 – hydroxynitrile lyases commonly used for Coprinus cinereus 1559 preparative application 948–953 Corallina officinalis 1559 – (R)-LuHNL 967 Corallina pilulifera 1559 – mechanistic aspects, and enzymatic cormycin A 768 promiscuity 967–970 cortisol 1255 – (S)-MeHNL 969 Corynebacterium glutamicum 1179, 1182 – (R)-PaHNL 967 Corynebacterium pseudodiphtheriticum 1172 – preparations 947 covalent catalysis 1746 – racemates resolution 973–975 6-C-perfluoroalkyl-D-fructose synthesis 883 – (S)-SbHNL 969, 970 CPMO-type enzymes, phylogenetic – transhydrocyanation 964–967 relationship of 1465 (R)-cyanohydrins synthesis 950, 954 CPO-catalyzed oxidation, of activated primary 4-cyano-3-hydroxybutyric acid esters alcohols 1359, 1360 – production of 1838 Criegee intermediate 1462 2-cyano-2-phenyl-1-hexanol 312 – stereoelectronic requirements 1462 2-cyanopyridine 825, 826 crispine A, deracemization of 1544 3-cyanopyridine critical assessment of structure prediction – chemical alkaline hydrolysis 523 (CASP) 94 cyano-substituted cyclohexanone crosslinked enzyme aggregates (CLEAs) 230, – stereodivergent oxygenation of 1464 952, 972 5-cyanovaleramide 822 crosslinked enzyme colloids (CLECs) 952 5-cyanovaleramide synthesis 522 crosslinking of enzyme aggregates cyclic amide compounds, metabolisms 665 (CLEAs) 556 cyclic amide-hydrolyzing enzymes, substrate Cryptococcus laurentii 837, 1614 specificities 653 Ò crystalline cellulose (Avicel ) 954 cyclic-amide metabolism 652 crystallization 212, 213, 262 cyclic amides, enantioselective C-terminal amide bond, selective hydrolysis 570–574 cleavage 622–628 cyclic amide transforming enzymes diversity Cunninghamella blakesleena 1301 and versatility, applications 665–669 Cunninghamella echinulata 1389 cyclic esters and derivatives, enantioselective Cupriavidus necator 1499 hydrolysis 299 cyanide 9 – resolution of cyanide-catalyzed benzoin condensation 919 ––azlactones 301 cyanide dihydratases (CDH) 545 ––lactones 300 cyanide hydratases (CH) 545 ––thiazolin-5-ones 302 8-cyano-FMN 1119 cyclic imide-hydrolyzing enzymes, substrate cyanogenesis 948 specificities 667 cyanohydrins 263 cyclic imide metabolizing enzymes, – cleavage and formation 947–981 applications 666 – cyanides safe handling, experimental cyclic L-amino acids 1197 techniques 977–981 cyclic oxidation racemic mixture, – enantiomerically pure cyanohydrins, follow- deracemization of 1539 up chemistry 975–977 cycloaddition antibodies 1756, 1757 – (S)-HbHNL 968, 969 cycloalkane oxides 406 – HNL-catalyzed addition of hydrogen cyanide cyclobutanols 322 to ketones 955–964 cyclodextrin 454 1952j Index

cyclodextrin glucanotransferases decarboxylation 850 (CGTases) 454 de-epimerization 58 – produces cyclodextrins 1822 degenerate oligonucleotide gene shuffling cyclodextrins 399, 514, 1822 (DOGS) 137 – production process 514 degree of functionalization 863 cyclohexanone, desymmetrization of 1469 dehydratases 486 cyclohexanone monooxygenase dehydroquinase 484 (CHMO) 168, 1556 – types I/II mechanisms 484 – oxidative desymmetrization catalyze 169 de novo protein design 102 – putative binding pocket, illustration of 170 3-deoxy-D-arabino-heptulosonic acid 7- cyclohexanone monooxygenase phosphate (DAHP) 875 (CYMO) 1548 – synthetic approaches to 876, 883 – from Acinetobacter NCIMB 9871 1-deoxy azasugars, stereodivergent (CHMOAcineto) 1448 synthesis 890 cyclohexenone monooxygenase (CMO) 1547 6-deoxy-6-butylaminosorbose 1592 2-cyclohexenones 1147 11-deoxycortisol hydroxylation 1258 cycloketone converting enzymes 1453 deoxypolyoxin C 905 cycloketone precursors, oxygenation of 1456 deoxyribonucleosides synthesis 862 cyclo-olefinic precursor 892 2-deoxy-D-ribose 5-phosphate aldolase cyclopentadecanone monooxygenase 1451 (RibA) 861 cyclopentadiene 1305 – catalyzed sequential aldol additions 863 cysteine peptidases 682, 683, 687 – metabolic reaction 861 cysteine residue, catalytic role 562 – synthetic applications 861 cysteine sulfinic acid (CSA) 797 2-deoxyribose 5-phosphate aldolase cytochrome c 1557, 1752 861–864, 1022 cytochrome P450-catalyzed oxidation, of deoxyribose-5-phosphate aldolase phenylacetylenes 1314 (DERA) 995 cytochrome P450-catalyzed 2-deoxy-D-ribose synthesis 475 oxyfunctionalization 1275 1-deoxysugar phosphates synthesis 931 cytochrome P450 monooxygenases 91, 92, 1-deoxysugars synthesis 900 98, 1229, 1270, 1313, 1555, 1558, 1597 D-ephedrine 991 – binding site of 105 dephosphorylations cytotoxic pancratistatin pharmacophore 894 – enzymes used in 1005 – of a range of phosphoproteins 1010 d – in vivo 1009 Daicel, enzyme production 1881 deracemizations 52, 1385–1391, 1539, – contact information 1881, 1882 1617, 1618 – enzyme screening sets 1883 – of amino acids 789 D-amino acid dehydrogenase-catalyzed – cyclic 53 reductive amination 1195, 1196 – enantiomeric excess 1541 D-amino acid oxidases (D-AAO) 1536, 1840 desaturases 1719 D-amino acids 795, 796, 1196 design, of new enzyme catalyzed reactions. – synthesis 1195 See protein engineering Danaus chrysippus 341 designer cells 4, 32, 1183, 1199, 1210, 1219 Darwinian experiment 119 desymmetrization reactions 8, 9 D-aspartate transaminase 848, 849 desymmetrizations 1379 D-aspartic acid 993 D-gluconic acid 1051 D-cyclohexylalanine 1196 D-gluconolactone 1051 deacetylipecoside synthase 770 D-glucosaminate dehydratase 768, 769 deacetylisoipecoside 770 DHA/DHAP-utilizing aldolases 877–901 deacetylisoipecoside dopamine-lyase 770, 771 – dihydroxyacetone phosphate (DHAP) DEAE ion exchange chromatography 623 synthesis 895–898 deaminase 767 – fructose 1,6-bisphosphate aldolase 879, 880 decarboxylase reaction 922 – fructose 6-phosphate aldolase 898–901 Index j1953

– fuculose 1-phosphate aldolase 880, 881 dihydroxylation 1308 – product diversity 882–895 L-threo-3,4-dihydroxyphenylserine – rhamnulose 1-phosphate aldolase 880, 881 (DOPS) 907 – stereoselectivity 882–895 diiron hydroxo-bridged center 1497 – synthetic strategies 882–895 Diiron monooxygenases (DIMOs) 1496 – tagatose 1,6-bisphosphate aldolase 880, 881 diisobutylaluminum hydride (DIBAlH) 975 – transaldolase 898–901 N,N-diisopropyl-4-hydroxypentanamide 319 DHAP aldolases, applications 882, 889, 902, diisopropyl phosphofluoridate (DFP) 1004 680, 691 diabetes 1004 1,3-diketone 1738 a,a-dialkylated a-azido carboxamides N,N-dimethylacetamide 1817 – amidase catalyze resolution 621 (RS)-2,2-dimethylcyclopropane diaminoalkanoate dehydrogenases 1178 carboxamide 569 diaminopimelate epimerase 1618, 1625, rac-2,2-dimethylcyclopropane carboxamide, 1626 resolution 569 diaminopropionate ammonia-lyase 768 dimethylformamide (DMF) 710 1,4-diarylbutan-1-one 1741 2,4-dimethyl-3-pentanol 319 diastereomeric substrate–catalyst cis-2,2-dimethyl-3- complexes 59 phenylcylopropancarbonitrile 537 diastereomer mixtures, kinetic 1,5-dimethyl-2-piperidone 824 resolution 907 2,5-dimethylpyrazine 1596 diastereoselective L-tyrosine decarboxylase dinitriles, mono-hydrolysis 551, 553 (L-TyrD) 906 dinitrodibenzyl 1591 diastereoselectivity 45 2,20-dinitrodibenzyl synthesis 1592 meta-dibromobenzene 1515 diol dehydratase 472, 473 3,5-dichlorobenzaldehyde 925 diol dehydrogenases 1513, 1515 3,4-dichloroisocoumarin 680 1,4-diols 1376, 1377 Diels–Alder reactions 876, 877, 1233, 1756 diols, oxidative lactonization of 1326 diethanolamine 1011 dioxygenase activity 1273, 1515 (diethylamino)sulfur trifluoride (DAST) 977 dioxygenase regioselectivity 1492 2,3-dihydrobenzo[b]thiophene 1558 dioxygenases 1240, 1308, 1491, 1509, 1555 dihydrocarvone, regiodivergent BVMO- – iron(II)/a-keto acid-dependent dioxygenases mediated oxygenation of 1465 (KGDO) 1241–1244 cis-dihydrodiols 1489, 1510 – Rieske cis-diol dioxygenases 1241 1,2-dihydronaphthalene 1313 dipeptide H-Tyr-Arg-OH dihydropyrimidinase – CPD-Y/PAF catalyzed synthesis 624 – partially purified fraction 656 diphenylacetylene (DPA) 1518 dihydroxyacetone (DHA) 895, 1020, 1021, diphenyl phosphonates 1745 1023, 1024 Diplodia gossypina 1297 dihydroxyacetone phosphate dipole moment 779 – analogs 898 directed evolution – enzymatic in situ generation 896 – basic principles and challenges 121, 122 – oxidative enzymatic generation 897 – engineering enzyme stability 156–160 dihydroxyacetone phosphate (DHAP) 877, – engineering enzyme stereoselectivity 160 895–898, 1004 ––CC Bond-Forming Enzymes 172–174 dihydroxyacetone phosphate dependent ––hydrolases 161–167 aldolases 878 ––oxidases 167–170 dihydroxyacetone synthase (DHAS) 938 ––reductases 170–172 dihydroxy acid dehydratase (DHAD) 477, 478 – of enzymes 162, 163 – tautomerization in 478 – gene mutagenesis methods 122 2,3-dihydroxy-2,3-dihydrobenzoate (2,3- ––comparative studies 143–148 CHD) 930, 934 ––computational guides 149–152 1,3-dihydroxy ketones 930 ––general guidelines 140–143 2,3-dihydroxy-4-ketovaleric acid 937 ––recombinant methods 135–139 1954j Index

–– saturation mutagenesis 128–135 – 1,3- and 1,4-diols 60 –– whole gene methods 122–128 – biocatalyzed-mediated 59 – history of 119–121 – classification of 59 – purpose of 119 – de-epimerization of 59, 60 – screening, steps 121 – of diastereomeric mixtures 46 – screening vs. selection 152–156 – diastereomers 58–60 disaccharide mimetics synthesis 892 – of diols 1789–1791 discovery, enzyme 81, 82 – types of 57, 59 a,a-disubstituted amino acid amides dynamic kinetic resolution (DKR) 46, 263, – examples 608 577, 1385, 1461, 1539, 1778 – resolution 607 – allylic alcohols 1791, 1792 a,a-disubstituted a-amino acids – amines 1796–1801 – applications, examples 576 – of amino acid derivatives 1613 a,a-disubstituted cyanohydrin acetates – a-amino acid esters 1795, 1796 – kinetic resolution 974 – axially chiral allenes 1801, 1802 2,2-disubstituted 1,3-diols 342 – b-halohydrins 1787–1789 D-2-keto-3-deoxy-6-phospho-gluconate (KDPG) – chemoenzymatic DKR of sec-alcohols 1782 aldolase 172 – a-chiral center 56 D,L-amino acids, deracemization of 1540 – cyanohydrins 1786, 1787 DL-pipecolic acid, deracemization of 1540 – 1,2-diarylethanols with PSL 1785 DL-proline, deracemization of 1540 – enzymatic, applicability of 55 D-lysine 5,6-aminomutase 1666 – fluorinated sec-alcohols 1781 D-mandelic acid, degradation of 1421 – general scheme of 55 DmpA’s active-site residues 602 – heteroaromatic alcohols 1785, 1786 DNA-abzymes 1748, 1752 – hydrolysis reactions 1802, 1803 DNA-binding transcriptional regulator 594 – polymerization, chiral polyesters 1810 DNA cleavage 1749 – primary alcohols 1793–1795 DNA fragment 662 – rac mixture, dynamically racemized 263 DNA-hydrolysis 1749 – sec-alcohols catalyzed by lipase and Ru – by 3D8 antibody 1750 complexes 1780 DNA-hydrolyzing antibodies 1751, 1752 – sec-alcohols using CALB and Shvo’s – cytotoxicity 1752 complex 1779 DNA polymerase 136 – secondary alcohols with two large DNA sequencing techniques 90 a-groups 1784, 1785 DNA shuffling 29, 120, 136, 143, 147, 157, 158 – using vanadyl sulfate and lipase 1782, 1784 DNA-specific autoantibodies, with dynamic kinetic symmetric transformation autoimmune pathologies 1751 (DYKAT) DNA synthesis 137 – ThrA-based preparation 906 dodecanoic acid, hydrolysis rates 556 donor-acceptor concept 933 e dopamine 770 EC 4. See lyases dopamine b-monooxygenase 1228 E. coli b-galactosidase, structure of 144 dorzolamide 324, 325 E. coli XL1-Red mutator strain 167 downstream processing 229 EDDS lyase 755, 756 D-p-hydroxyphenylglycine 21 efficiency quotients 512 D-pseudoephedrine 991 elastin-like polymer (ELP) 1824 D-ribulose-1,5 biphosphate 1025 electron-rich heteroaromatic rings, oxidation DSM process of 1512 – for production of amino acids 833 electrophilic reactions 92 – for production of amoxicillin 832 1,2-elimination reactions 1756 – for production of cefalexin 830 b-elimination reactions 468 DuPont erbicide azafenidine 521 enantioconvergent processes (ECPs) 54 dynamic kinetic asymmetric transformation (R)-enantiomer 923 (DYKAT) 56, 328, 906 enantioconverting reaction 403–406 Index j1955 enantiomerically pure D-amino acids 594 – advantage, using haloperoxidases and 1580 enantiomerically pure cyanohydrins – comparison of chemical with 1580, 1581 – follow-up chemistry 975–977 – flavin-dependent halogenase, use of 1581 enantiomerically pure L-/D-unsaturated amino – regioselectivity, and stereospecificity 1579, acids 1580 – multi-gram synthesis, optimized – tryptophan halogenases, amidase-based process for 589 egioselectivity 1580, 1581 enantiomeric ratio 51 – of unactivated methyl groups 1581 enantiomerization 1617 enzymatic kinetic resolution process 607 – synthesis by 1617, 1618 enzymatic modification, of peptides 737, 738 enantiopure cyanohydrins 947 enzymatic organic synthesis, cofactors 11 enantiopure a-H-a-amino acids enzymatic peptide synthesis 622, 729 synthesis 575–607 – fragment condensation 732–737 – bacterial leucine aminopeptidases, protease – planning and process development 729 independent functions 593 – selected examples 734 – M17 family, leucine aminopeptidases – stepwise chain elongation 729–732 588–594 enzymatic phosphoryl transfer – D-selective a-H-a-amino acids amide reactions 1007 hydrolase 594–607 enzymatic polyamide synthesis 1843 – L-selective a-H-a-amino acids amide enzymatic polymerizations 1842 hydrolase 579–588 enzymatic processes, greenness of 1849 enantiopure 2-hydroxy ketones synthesis 939 enzymatic reductions, synthetic applications enantioselective amidase hydrolysis 568 of 1081 enantioselective biotransformations 536 – bulky ketones reduction, with two large enantioselective conversions 552–554 substituents 1085–1090 enantioselective fungal epoxide – ketones reduction, with two small hydrolases 398 substituents 1081–1083 enantioselective PAL variants, directed – reduction of keto esters 1095–1098 evolution of 147 – reduction of more complex cyclic enantioselective sulfatase 54 ketones 1090–1092 enantioselectivity 45, 363 – reduction of multisubstituted, and hydroxy- endopeptidases 677, 683 substituted acetophenone enoate reductases 1135–1138 derivatives 1083–1085 enolase enzymes 1718 – reduction of steroid ketones 1092–1095 enol-CoA hydratase 1. See (S)-specific enzymatic resolution processes, enoyl-CoA hydratase enantioselectivities 15 enol-CoA hydratase catalyzes dehydration 468 enzymatic selectivity, types of 45 enone enantiomers, lipase-catalyzed enzymatic surface hydrolysis 1814 resolution 507 enzymatic synthesis 1808 Enterobacter cloacae 1129 – historical development of 18 Entner–Doudoroff pathway 873, 875 enzymatic synthesis, of D-amino acids 1614 EnzBank, enzyme production 1883 enzymatic transesterification 1818 – contact information 1884 enzymatic transformations 37 – hydrolases 1884 – in organic synthesis 44 – miscellaneous enzymes 1885 enzyme activity unit 191 enzymatic acyloin condensations enzyme (auto)antigen 1742 – chemoselectivity 922, 923 enzyme catalysis 38 – stereoselectivity 923, 924 – applications of 38–39 enzymatic Baeyer–Villiger – for C¼C double bond reductions 6 oxygenations 1453, 1457, 1469 – drug synthesis, novel retrosynthetic enzymatic decarboxylation mechanism 921 approaches in 34–37 enzymatic esterification, polycondensation – dynamic view of 106 reactions 1808 – hybridization of 31 enzymatic halogenation reactions 1579, 1580 – molecular catalysts 22 1956j Index

– in organic synthesis 3–4 enzyme nomenclature 5, 1004, 1167 – potential of enzymes –– advantages and drawbacks 14–17 – biochemical properties of 104 –– coenzymes/cofactors, overview of 11–13 – catalyze 43 –– EC numbers, overview of 5–11 – categorization of 6 –– enzymatic reactions, factors affecting 13 – characterization of 18 –– three-dimensional structure 4–5 – databases of 27 – principle of 67 – design see enzyme design – redox processes 7 – directed evolution 162, 163 – tailor-made recombinant whole-cell catalysts, – discovery, challenge of 82 applications of 32–34 – discovery of 81 enzyme-catalyzed acyloin condensations – in DNA sequence 91 – advantage 923 – evolution of 92 enzyme-catalyzed aldol reactions 898 – function 67, 69 enzyme-catalyzed enantioselective propion – immobilization 234, 556 formation 929 – industrial applications of 1837 enzyme-catalyzed enantioselective reductive – industrial, performance profiles of 71 amination 1165 – isolation 191 enzyme-catalyzed kinetic resolutions 1777, – modeling, computational methods of 90 1778 – nomenclature 5, 1004, 1167 – theoretical yield 1778 – production 191 enzyme-catalyzed (R)-PAC syntheses 924 – promiscuity 38 enzyme-catalyzed reactions 34, 92, 661 – purification see purification of enzymes – drawback 972 – screening, strategies for 27 – sequence 661 – screening system 74 enzyme-catalyzed transesterification – sequence-structure-function relationships – of polymers 1819 of 92 enzyme classification (EC) 68 – by solid fermentation, production enzyme-coupled approach 1337 process 193 enzyme design 89 – technology, scope of 219 – biochemical properties of 89 enzymes catalyzing reductive amination – challenges 104 reactions, biochemical properties of 1170 –– force field, system size, and simulation – D-amino acid dehydrogenases 1180 time 104 – diaminoalkanoate dehydrogenases 1178 –– nanomachines 105–106 – glutamate dehydrogenase 1177 – computational methods of 90 – L-amino acid dehydrogenases 1170, 1171 – data mining 90–92 – leucine dehydrogenase 1171, 1172 – docking 96–97 – L-lysine 6-dehydrogenase 1178, 1179 – enzyme structure, prediction of 94–95 – meso-a,e-diaminopimelate D- – high-resolution structure of 90 dehydrogenase 1179 – molecular dynamics simulations 97–99 – N-methyl- L-amino acid – molecular modeling and protein design 94 dehydrogenase 1180, 1181 – protein stability and solubility 95–96 – opine dehydrogenases 1181 – quantum chemical methods 99 – phenylalanine dehydrogenase 1172, 1177 – rational evolution 93–94 – relative activity values for 1173–1175 – solvent role – relative reaction rate for reductive amination –– hydration of enzymes 100 of 1176 –– in organic solvents 100, 101 enzymes catalyzing reductive amination, –– solvent-induced conformational synthetic applications of 1181–1183 changes 101, 102 enzymes discovery 67–82 –– stable/functional proteins, de novo design – activity-based screening 76–80 of 102–104 – enzyme screening enzyme membrane reactor (EMR) 23, 26, –– challenges 81, 82 225, 227, 866, 954 – exploiting functional sequence space 72 Index j1957

– gene mining techniques 74, 75 – enantioconvergent chemoenzymatic – historical overview 67–70 reactions 405 – ideal enzyme concept 70–72 – enantioconvergent reactions catalyzed – resources for 72, 73 by 403–405 – screening strategies 73, 74 – epistatic interactions operating 166 – sequence homology-based screening – hydrolytic kinetic resolution of 163 techniques 75, 76 – improvement by mutagenesis and enzymes, industrial application of 1841 evolution 400, 401 – applied in textile industry 1843–1845 – and other enzymes acting on epoxides 364, – aqueous polyamide dispersions, enzymatic 367, 368 synthesis of 1842, 1843 – reaction engineering 398–400 – poly(hexane-1,6-diyl adipate), enzymatic – synthesis of optically pure diol/epoxide large-scale production of 1842 using 392, 393 enzyme–solvent systems 97 – vs. halohydrin dehalogenases 369 enzymes oxidizing at sulfur 1553, 1554 – WT, fitness landscape featuring 166 enzymes oxidizing at sulfur and – WT, X-ray structure of 164 sources 1555 – yield 403 enzymes, stereoselectivity of 7 1,2-epoxyhexane 400 enzyme–substrate complex 96 error-prone polymerase chain reaction enzyme–substrate complexes 98 (epPCR) 120 enzyme thermostabilization – alcohol-mediated 123 – based on laboratory evolution 160 – dNTP substrate ratio 124 enzymic catalyst 869 – with iterative saturation mutagenesis (1R,2S)-ephedrine (ISM) 145 – chemoenzymatic synthesis 921 – NADPH-dependent aldo-keto reductase, epimerases 1609 thermostability of 158 – cofactor-independent, reaction – shot-gun method 123 mechanism 1618, 1619 – simplest random mutagenesis method 123 – syntheses using 1685–1687 – Taq-polymerase 124 epimerases acting on carbohydrates and – use of 157 derivatives 1637–1643 Erwinia chrysanthemi 159 epimerases, acting on carbohydrates and trans- D-erythrosphingosine synthesis 475 derivatives 1637 erythro/threo-isomers 904 epimerization Escherichia coli 72, 121, 695, 790, 824, 846, – at hydroxy-substituted carbons 1632, 1633 993, 1544, 1841 epimerizations 1610 esterase antibodies 1741 epoxidation – AChE abzyme 1742 – by oxidase 1589 – AE2mAb 1743 – of styrene 1595 – 9A8 mAb 1742–1745 epoxide 363 – A17 scFv antibody 1746 – alcohol dehydrogenases 366, 367 – 50D8 antibody 1742 – biocatalytic reactions involving 364 – monoclonal AE2 antibody 1742 – biocatalytic strategies 365 – MOPC167 antibody 1741 – carboxylase 364 – useful therapeutics against drug addiction – conjugation 365, 366 and 1745 – oxidation of alkenes 366 esterases 251–255, 1701, 1719 epoxide hydrolases 54, 159, 161, 1719 – Bacillus subtilis esterase BS2 166, 167, 252 – applications, to synthesis of chiral epoxides – catalytic cycle of 253 and diols 391 – enantioselectivity of 259–261 – assays 401–403 – esterase from Burkholderia gladioli – binding pocket and CAST sites A–F of 164 (EstB) 157 – catalyzing kinetic resolution of racemic – specific to lignocellulosic materials 1819, epoxides, yielding 395–397 1820 – conversion of meso-epoxides 406 ester hydrolysis 1741–1747 1958j Index

esterifications 1809 FAD enzyme styrene monooxygenase 1517 – in lipases processes 508–513 FADH2-dependent halogenases 1570–1572, esters 251 1576–1578 – application of 257 D-fagomine – enantioselective hydrolysis 504 – two-step synthesis 900 – irreversible synthesis 258 fatty acid-based esters, non-stereoselective – synthesis formation of 350, 351 –– reactions in organic solvents 256–258 – isopropyl palmitate 350 –– vs. ester hydrolysis 255, 256 – myristyl myristate 351 ethanolamine 771, 1011 fatty acid biosynthesis 486–489 ethanolamine ammonia lyase 771 fatty acid degradation, b-oxidation 489–491 ethionamide monooxygenase 1556 fatty acid esters 512 1-ethoxyvinyl 2-furoate 346 – production of 9 ethyl acetate 834 fatty acid synthase (FAS) 486 ethyl(dimethylaminopropyl)carbodiimide – via Claisen-type condensation 487 (EDC) 730 fermentations 554, 844, 1461 (S,S)-ethylenediamine disuccinate (EDDS) – to biotransformations 17 lyase 750 – to biotransformations using wild-type whole ethylenediaminetetraacetic acid 680 cells 17 ethylenediaminetetraacetic acid (EDTA) 586, – of enzymes 196 1446 –– extraction of enzymes 196 ethylene glycol (EG) 1813 –– liquid fermentation 196 N-ethyl-maleimide 680 –– solid fermentation 196 N-ethylmaleimide reductase 1124 –– ultrafiltration 198, 199 Eubacterium barkeri 1239 – historical development of 17–19 Eucodis Bioscience GmbH, enzyme production – immobilized form – b-lactamases 1888 –– wild-type whole cells 20, 21 – contact information 1885 – non-immobilized form – lipases 1886, 1887 –– wild-type whole cells 19 – phospholipases 1887 ferredoxin 1493 E-value 15, 145, 164, 168, 267, 286, 365, 375, feruloyl-CoA hydratase. See hydroxycinnamoyl- 382, 384, 391, 404, 508, 510, 836, 839, 1331, CoA hydratase lyase (HCHL) 1778, 1837 Fe-S-dependent serine hydratases 769 Evocatal GmbH, enzyme production five/seven-membered ring azasugars, – alcohol dehydrogenases 1890 stereoselective synthesis 890 – amino acid dehydrogenases 1890 flavin cofactor 1492 – contact information 1888 flavin-containing BVMOs – hydrolases 1891 – mechanism and catalytic cycle of 1441 – ketoreductases 1889 flavin-dependent halogenases, reaction – lyases 1891 mechanism for 1574, 1576 – fl NAD(P)H regeneration enzymes 1889 avin-H2O2 system 1554 Evonik Degussa 23–34, 351, 509, 662, Flavobacterium meningoseptum 703 835–851, 1070, 1185, 1186, 1207–1219, Flavobacterium saccharophilum 769 1421, 1686 flavoprotein monooxygenases 1277, 1498, exopeptidases 677 1499 expressed protein ligation, principle of 696 flexible electronic devices (FEDs), production extracellular enzymes, production of 1812 process 192, 193 fluidized-bed reactors 225 extradiol dioxygenases 1500 fluorescence accelerated cell sorting (FACS) extremophilic microorganisms 13 screenings 80, 155 fluorescence-labeled enantiomeric tyrosinal f substrates, synthesis of 156 B-factor iterative test (B-FIT) 135 fluorogenic compound 883 FAD-containing monooxygenase 1555 fluorophosphonates 1745 Index j1959

fluoropyruvate 867 gene of interest (GOI) 76 flurbiprofen 336 – transcription of 77 formate dehydrogenase (FDH) 1186, genetically modified organisms (GMOs) 195 1206–1208, 1420, 1443, 1880 genetically modified peptidases 709 – Candida boidinii 1421 genetic engineering 219, 694 free energy 1004 genetic selection, model system for free enzymes 24 enantioselectivity 154, 155 – development of 24–26 Genomes Online databases (GOLD) 75 Friedel–Crafts alkylation 760 genomic sequence analyses 534 fructose 1,6-bisphosphate aldolase genotype–phenotype linkages 155 (EC 4.1.2.13) 879, 880 gentisate 1,2-dioxygenase (GDO) catalyzes 1505 D-fructose 1,6-bisphosphate aldolase Geobacillus stearothermophilus 1172, 1179 (FruA) 864, 879 Geobacillus thermodenitrificans 1250 – catalyzed reactions 884 Geobacillus thermoglucosidasius A7 1499 – diastereoselectivity in 885 Geotrichium candidum 1391 – natural glycolytic substrate 879 7-geranyloxycoumarin 1308 fructose-1,6-bisphosphate 1- Germacrone 1301 phosphatase 1010 germacrone stereoisomers, epoxidation fructose-1,6-diphosphate aldolase 1022 of 1301 fructose 6-phosphate aldolase c-glutamyl transpeptidase 686 (EC 4.1.2.n) 898–901 9G4H9 antibody 1758 fructosyltransferases 454 Gibbs-free energy 1389 L-fucose, enzymatic synthesis 886 glucoamylase 516, 517 fuculose 1-phosphate aldolase 880, 881 gluconeogenesis 766 L-fuculose 1-phosphate aldolase (FucA) 880 Gluconobacter asaii 1379 fumarase 467, 473–475 Gluconobacter oxydans 1099, 1343, 1378, 1592 – application in organic synthesis 475 Gluconobacter suboxydans 17 fumarase C 474 glucosaminic acid deaminase 768 fumarases glucose – catalyze addition of water to fumarate – chemoenzymatic transformation of 1378 to yield (S)-malate 473 – enzymatic transformation of 10 – iso-mechanism in reaction with 474 glucose dehydrogenase (GDH) 1051, 1052, fumarate 1206–1208, 1217, 1880 – hydration/dehydration 474 glucose isomerase 219, 886 – malate production from 518 glucose oxidase 1346, 1347 fumaric acid 517 – copper metalloenzyme 1348 Fungal Cytochrome P450 Database 1230 – food and beverages 1348 Fusarium oxysporum 300 – glucose sensors 1348 Fusarium solani 1815 – for H2O2-free regeneration 1347 fused bicyclobutanones, regiodivergent – indirect electrochemical regeneration bio-oxidation of 1466 of 1347 fused cyclobutanones, regiodivergent glucose-1-phosphate 453, 1006, 1021 bio-oxygenation of 1464 glucose-6-phosphate 1006, 1021, 1022 fusion enzyme biocatalysts 1445 glucose-6-phosphate dehydrogenase (G6PDH) 1053, 1054, 1443 g glucosides 454 galactose oxidase (GalO) 883 glutamate dehydrogenase 1194, 1337 b-galactosidase (BGAL) 143 glutamate dehydrogenase catalyzed reductive b-galactosidase mutants 153 amination 1194 GalOx-substrates – in situ synthesis of L-glutamate as 1195 – selection of 1349–1351 – synthesis of L-6-hydroxynorleucine GARFT inhibitor 282 with 1194 geloenzymes 399 glutamate dehydrogenases 1177 gene mining 74, 75 glutamate mutase 1666, 1667 1960j Index

glutamate racemase 1618–1620 C-glycosidically linked azadisaccharide 892 – biochemical properties 1620, 1622 9-glycosylated KDN synthesis 871 – oligomeric state and kinetic parameters, glycosyltransferases 419, 428, 1713, 1820, comparison 1621 1822 – peptidoglycan primary structure 1620 – acceptor modifications tolerated by bovine – synthesis of D-amino acids with 1622–1624 b-1,4-GalT 441 glutamic:oxaloacetic transaminase (GOT) 796 – C- and N-glycoside formation catalyzed glutamic-pyruvic transaminase 781 by 452 glutaraldehyde 710 – cloning of genes coding for 442 glutaryl-7-aminocephalosporanic acid – coupling of b-1,4-GalT-catalyzed (7-ACA) 1588 galactosylation with 441 glutathione transferases 1719 – effect of organic cosolvents 443 glyceraldehyde enantiomers 882 – enzymatic synthesis of globotriose 443 D-glyceraldehyde 3-phosphate 879 – exploitation from bacterial pathogens for glycerol 1011 synthesis of 450 glycerol dehydratase (GDH) 472, 473 – galactosylation of ginsenoside 442 – transformation of glycerol into – glycosylation of vicenilactam catalyzed 3-hydroxypropionaldehyde, by 451 general reaction mechanism 472 – isolated yields of globotriose glycerol dehydrogenases (GDHs) 1331–1334 derivatives 444 – applications of 1334 – key enzyme–substrate interactions between – 1,2-diols catalyzed, oxidation of 1334 sugar acceptors and 445 – rac-phenylethandiol, kinetic resolution – of Leloir pathway 429–432 of 1331 – from microbial sources 448–453 glycerol oxidase 1363 – modified TDP-deoxysugars in glycerol phosphate 1011 actinomycetes 430 glycerol phosphate oxidases (GPOs) 896 – non-Leloir glycosyltransferases 453, 454 – method 884 – novel b-1,4-GalT-catalyzed reactions 446 glycine 1554 – relative rates of GalT-catalyzed glycine-dependent aldolases galactosylation reactions with 439 – enzyme-specific kinetic – ribbon diagrams of different GTs folds 431 stereoselectivity 903 – substrate engineering of a-1,4- – thermodynamic equilibration 903 GalT-catalyzed reactions 447 glycine-utilizing aldolases 901–908 – substrate promiscuity of b-1,4-GalT glycoconjugates 417 from 449 – biologically active 418 – substrate specificity 438, 439, 441–448 glycolaldehyde 900 – sugar nucleoside phosphates, synthesis – ethylene glycol, oxidation of 1366 of 432, 436–438 – self/crossed-aldol reactions 901 – synthetic applications 438, 439, 441–448 glycolate oxidase (GlyOx) 1354 – three-dimensional structures 432 glycoprotein 471, 1558 – transfer of C2-modified galactose catalyzed glycosidase antibodies 1754 by 440 glycosidase inhibitors 1003 – VinC-tolerated non-natural acceptorsy 451 glycosidases 419, 1003, 1713, 1715, 1820 glycosynthases 427, 428, 1713, 1714, 1715 – catalytic mechanism 420 glyoxylic acid 903 – engineering strategies 419 GMC-oxidoreductase 967 – formation of glycosidic bonds 423–427 GMO enzymes for industrial use 195 – glycosidases inhibitors 421 Godo Shushei, enzyme production – hydrolysis of glycosidic bonds 422, 423 – contact information 1891 – inverting glycosidases 420 – hydrolases 1892 – retaining glycosidases 421 grafting reactions, enzymes for 1818 – synthetic applications of 421 gramicidin S synthetase 1 1612 b-glycosidases 1713, 1714 gram-positive bacteria 546 glycoside hydrolases 419 granulocyte serine peptidases 689 Index j1961

Grignard reagents 1004 Henry-type cyclization 887 4-guanidinophenyl esters 717, 718 – aminocyclitol precursors preparation 888 guanosine-50-monophosphate (50-GMP) 29 hepatitis C viral protease inhibitors 1544 – structures of 1545 h heteroarene substrates, dihydroxylations halogenated metabolites 1574 of 1511 halogenation 1569 heteroatom-containing ketones 1471 – of tryptophan 1577 heterocyclic ketones 952 halohydrin dehalogenases 61, 151, 369, 370, Hevea brasiliensis 26, 38 1217, 1602 hexane-1,6-diol 1842 – from Agrobacterium radiobacter 150, 370 hexosyltransferases 1021 – cascade reactions using 384–386 5-hexyl-cyclopent-2-enone 1457 – catalyzing dehalogenation of higher-carbon sugars, generation 892 chloroacetone 387 high-fructose corn syrup (HFCS) 219, 516, – characteristics 370 1655, 1656, 1685 – classification 370 high-level constitutive expression (HCE) – discovery of 371–373 promoter 605 – improvement, by mutagenesis and high partition coefficients 979 evolution 381–383 2-His-1-carboxylate facial triad 1271 – protein crystallography on 370 2-His/Glu facial triad family, oxygen – reaction mechanism 369, 371 activation 1272 – ring-closure reactions 373–376 histidine ammonia lyase 758 – ring-opening reactions 376–381 histidine degradation pathway 477 – use of 1838 histidine imidazoles 1238 – yield 383, 384 historical development of haloperoxidase-mediated alkyne – enzymatic synthesis 18 oxidation 1314 – fermentations 17–19 haloperoxidases 384, 1553, 1555, 1576 – transformations 22, 23 a-H-a-amino acid amide HLADH-catalyzed kinetic resolution 1374, – enantioselective hydrolysis 578 1375 – racemase 578 HLADH-catalyzed lactone-formation a-H-a-amino acids, applications 576 from 1376, 1377 haptens 1737 H2O2/catalase system 897 a-H-a-azido carboxamides 621 Hock cleavage 1312 HbHNL-catalyzed cyanohydrin cleavage 968 homodimeric coiled coil, thermostability HCN of 102 – enzyme-catalyzed addition 966 b-homoglycine (H-b-hGly-OH) 614 – hydroxynitrile lyase catalyzed addition to homologous proteins 102 aldehydes 953–955 homology modeling 102 heavy metals 680 horse liver alcohol dehydrogenase heme-containing monooxygenase (HLADH) 964, 1328 P450cam 1294 – stereoselectivity 1330 heme-containing proteins 1553 – substrates selection 1329 heme metallo monooxygenases 1229 horseradish peroxidase (HRP) 156, 1557 – cytochrome P450 monooxygenases – aerobic and anaerobic 1549 1229–1233 horse-radish peroxidase (HRP) 1548 – heme peroxidases 1233, 1234 HotSpotWizard 152 heme monooxygenases harbor 1274 HPLC methods 953 heme peroxidases 1356 2-HPP derivatives synthesis 928 hemiaminals 323 human P450 monooxygenases 1300 (S)-hemisuccinate, hydrolysis 510 D-hydantoinase hemoabenzymes 1553, 1554 – cyclizing function 662 hemoglobin 1557 D-hydantoinase 656, 657 Henry reaction 38 – gene sequence 656 1962j Index

L-hydantoinase 657, 658 hydrolases 11, 258, 260, 261, 779, 1289 D-hydantoinase process – enzyme catalysis reactions 8 – developments 661 – kinetic resolution (KR) enantioselectivity hydantoinases, processes using 839–841 of 262 hydantoin racemase 660, 1628, 1629 hydro-lyase, catalyzed reaction 473 hydantoins 839 hydro-lyases 467, 473 – biocatalytic dynamic kinetic resolution – catalyze addition of water 468 of 33 hydrolysis – D-N-carbamoylase 658, 659 – of amides 832 – L-N-carbamoylase 659 – of benzoyl ester of cocaine 1745 – cyclic amide transforming enzymes diversity – of 2-cyanopyrazine to pyrazine-2-carboxylic and versatility, application 665–669 acid 825 – D-stereoselective hydrolysis of 21 – and formation of amides 826–839 – D-hydantoinase 656, 657 – and formation of peptides 841, 842, 844, 845 – L-hydantoinase 657, 658 – of glutaryl-7-aminocephalosporanic – hydantoin rasemase 660 acid 827 – hydantoin-transforming enzymes – of 2-methylglutaronitrile 824 biotechnology 660–663 – of nitriles to acids 824–826 – hydantoin-transforming enzymes, structural – of penicillin G 829 analysis and protein engineering 663–665 – of phospho-enzyme, acidic pH 1011 – hydrolysis and formation 651–669 – of p-nitro-a-glucopyranoside 1755 – microbial hydantoin metabolism, application – of pre-pro-insulin 843 to biotechnology 651–656 – of pseudosubstrates by 9A8 1743 hydantoin-transforming enzymes – of vinyl acetate 1716 biotechnology 660–663, 669 hydrolytic reactions, in lipases – D-amino acid production 660, 661 processes 503–508 – L-amino acid production 661, 662 hydrolytic surface modification 1824 – b-amino acid production, application 663 hydroperoxides 1312 – N-carbamoylase, application 663 hydrophobic analogs, enzymatic – hydantoinase, application 662, 663 synthesis 886 – hydantoin racemase, application 662 hydrophobic ibuprofen methoxyethyl ester 504 – structural analysis, and protein hydrophobic substrate interface 101 engineering 663–665 hydrophobic substrates, bioavailability 555 hydratases. See hydro-lyases hydroquinone 1,2-dioxygenase (HDO) 1505 1,2-hydratases 469 b-hydroxy a-amino acids, asymmetric hydratase-tautomerase bifunctionality 483 preparation of 17 hydration/dehydration reactions 468 hydroxyacetone 900 hydration of nitriles 822 2-hydroxyacetophenone derivatives hydration reactions, b-oxidation of fatty synthesis 938 acids 488 2-hydroxy acid adduct 922 hydrazones, oxidative coupling of 1550 a-hydroxy acid amide DL-mandelic acid hydride-transfer 1409 amide 619 hydrocarbon monooxygenase 1556 hydroxy acid amides, enantioselective hydrocyanation process, non-immobilized hydrolysis 618–620 enzymes 26 (S)-3-hydroxyadamantylglycine 1194 hydrogel precursor, oxidation of 1549 3-hydroxy-a-ionone 1255 hydrogen atom abstraction (HAT) 1362 2-hydroxy aldehydes, L-configured hydrogen bonding 97 enantiomers 881 hydrogen peroxide 1227, 1591 2-hydroxy aldehydes, with hydroxypyruvate, – degradation 1591 TK-catalyzed reaction 940 – reduction of concentration by catalase 1591 b-hydroxy-a-amino acids 902 hydrogen peroxide-dependent hydroxyamino diacids, preparation 905 halogenases 1569, 1570 2-hydroxy-1-arylethan-1-ones 939 hydrolase-catalyzed processes 8 p-hydroxybenzoic acid esters 518 Index j1963

2-hydroxy-b-ionone 1254 – for organic synthesis 949 4-hydroxy-b-ionone 1254 – Prunus mume HNL (PmHNL) 953 3-hydroxybutyraldehyde 1024 – (R)-selective HNLs 948–951, 953, 954 3-hydroxy carbonyl compounds 857 – (S)-selective HNLs 951–953, 955 hydroxycinnamoyl-CoA hydratase lyase – used for preparative application 948–953 (HCHL) 491, 492 hydroxynitrile lyases (HNLs)-catalyzed hydroxydiamino acids, preparation 905 biotransformations 2-hydroxy-4-dienoate hydratases 478–482 – applications 981 b-hydroxy-isobutyric acid (3-HBA) 518 – catalysis in aqueous medium 978 b-hydroxy-isobutyric acid production 519 – catalysis in biphasic medium 979, 980 (2S,3R,4S)-4-hydroxyisoleucine preparation 877 – catalysis in organic medium 978, 979 2-hydroxy-3-ketobutyric acid 937 – experimental techniques 977–981 4-hydroxyketoglutarate preparation – transhydrocyanation for HCN – by direct GlcA-catalyzed synthesis 875 generation 980, 981 – by racemate resolution 875 a-hydroxynitriles. See enantiopure b-hydroxyketones cyanohydrins – 2-deoxyribo-5-phosphate aldolase (DERA)- b-hydroxynitriles 61, 318 catalyzed synthesis of 1369 2-hydroxypent-2,4-dienoate hydratase hydroxylases 1719 (HPDH) 482 hydroxylation 2-(4-hydroxyphenoxy)propionic acid – of nicotinate 1240 (HPOPS) 1590 – of nicotinic acid 1590, 1591 – oxidase catalyzed synthesis of 1590 – of 2-phenoxypropionic acid (POPS) 1590 D-p-hydroxyphenylglycine 575, 660 – of racemic a-ionone 1254 – decarbamoylation 661 – reaction, catalyzed by living whole – synthetic process 661 cells 1590, 1597 DL-5-(p-hydroxyphenyl)hydantoin 11b-Hydroxylation of 11- – D-stereospecific hydrolysis 661 deoxycortisol 1257 hydroxyproline epimerase 1618 hydroxyl-containing ketones 5-hydroxypyrazine-2-carboxylic acid 825 – rearrangement of 1455 3-hydroxypyruvate 765 3-hydroxy-3-methylglutaryl coenzyme A hydroxyquinol 1503 – inhibitor of 171 hydroxysteroid dehydrogenases 4-hydroxy-3-methyl-2-keto-pentanoate aldolase (HSDHs) 1335 (HkpA) 877 2-hydroxymethyl-5-methylpyrazine 1596 i b-hydroxy-n-butyric acid 519 ideal enzyme, identification of 697, 698 – production 140 Idiomarina loihiensis 762 6-hydroxynicotinate hydroxylase 1591 IDS lyase 756 6-hydroxynicotinate, synthesis of 1590 Ile151Thr 30 hydroxynitrilase 993 IMEnz engineering, enzyme production hydroxynitrile lyase-catalyzed cyanohydrin – contact information 1892 formation – thermostable proteases 1892, 1893 – aldehydes R-CHO as substrates 956–963 10,40-imino tautomer formation 922 – methyl ketones R-CO-Me as substrates immobilization-like systems 24 for 965, 966 immobilization method 954 hydroxynitrile lyases 61, 947, 948, 1720 immobilized enzymes 191 – application 947 – benefits 972 – Arabidopsis thaliana (AtHNL) 949 immunization, by TSA 1738 – catalyzed addition, of hydrogen cyanide to immunoglobulins 1737 ketones 955–964 incorporating synthetic oligonucleotides via – diastereoselectivity 974 gene reassembly (ISOR) 138 – Hevea brasiliensis HNL (HbHNL) 952 incremental truncation for the creation of – improvement by enzyme engineering, hybrid enzymes (ITCHY) 137 enzyme stabilization 970–972 indole oxidation 1549 1964j Index

indolizidine-type glycosidase inhibitor ion-exchange chromatography 1546 castanospermine 870 b-ionone 1254, 1255 indolocarbazole compounds 452 ionones, oxyfunctionalization of 1300 industrial application, of cyclohexanone iron-sulfur-containing aconitase 476 monooxygenase 1594 isobutyric acid 519 industrial biotransformations, for carbonyl isolated enzymes reduction 1206–1208 – in immobilized form 23, 24 industrial chemical production 89 – in redox process 32 industrial enzymes – transformations, historical development – flowchart of use 27 of 22, 23 – processes 1837 isoleucine 768 industrial enzymes for chemical isomaltulose synthase 1671, 1672 synthesis 191 isomerases 1609 industrial esterification processes – enzyme catalysis reactions 10 – using lipases 509 – processes 1685 industrial processes 25–27, 161, 171, 218, isomerization 234, 384, 575, 752, 863, 1101, 1217, – reaction for production of palatinose 1689 1506, 1643 isomerization reactions 1609, 1757 industrial-scale chemical synthesis 1849 iso-octane 400 infectious diseases 1761, 1762 isopenicillin N epimerase 1631, 1632 Ingenza system for deracemizing amines 168 isopentenyl-diphosphate D-isomerase 1660, inosine-50-monophosphate (50-IMP) 29 1661 50-inosinic acid monophosphate isoprene – synthesis of 30 – microbial oxidation of 1295 inositol monophosphatase 1010 isopropanol 1050, 1051 in situ product removal (ISPR) 230 (3S)-3-isopropenyl-6-oxoheptanoate 1306 insoluble enzymes, alternative reactors for 225 2-isopropenylpropane-1,2,3-triol 343 insulinotropic 4-hydroxyisoleucine isopropylamine 801, 850 – enzymatic synthesis 877 (R)-isopropylidene-glyceric acid 1587, 1588 insulin production 841–844 – synthesis of 1588 integrin a(v)b(3) 1739 (R)-isopropylidene-glycerol 1587, 1588 intein-CBD (chitin binding domain) fusion – chemical synthesis 1588, 1589 protein 697 isopropyl palmitate 350 intein-mediated protein ligation 696 isoquinoline alkaloid 770 International Union of Biochemistry (IUB) 68 ISOR, schematic representation of 138 International Union of Pure and Applied isotope-labeled N-acetylneuraminic acids Chemistry (IUPAC) 68 synthesis 867 intradiol dioxygenases 1500 DL-isovaline amide 608 intramolecular lyases 1609 iterative protein redesign and optimization intramolecular oxidoreductases 1609, 1646, (IPRO) 151 1647, 1687, 1688 – generalization of 152 – biochemical properties 1653–1655 – steps 152 – D-arabinose isomerase 1648–1650 iterative saturation mutagenesis (ISM) 132, – D-xylose (glucose) isomerase 1652, 1653 134, 145, 146, 148 – L-arabinose isomerase 1651, 1652 – protein properties 148 – reaction mechanism 1653–1655 – thermostabilization of proteins 135 – syntheses using 1687, 1688 – triosephosphate isomerase 1647, 1648 k intramolecular S ! N acyl transfer kanamycin nucleotidyl transferase 120 reaction 695 Kanegafuchi Chemical 21 intrasequential cofactor regeneration 1338 KcdA chemoselectivity 926 inversion strategy 885 Kemp elimination 31, 103, 1717, 1722, 1723 invertase process 516 KER-mutant, enantioselective reduction 171 iodoacetate 680 2-ketoacid decarboxylases 921 Index j1965

2-keto acids – reduction of more complex cyclic – reductive animation of 1420 ketones 1090–1092 ketoadipinyl-7-aminocephalosporanic – reduction of steroid ketones 1092–1095 acid 1587 – with two small substituents 1081–1083 2-ketobutyrate 796 2-keto-4-phenylbutanoate 1192 5-keto-4-deoxy-D-glucarate (5-KDG) 478 ketoreductases 1326 2-keto-3-deoxygluconate (KDG) 864 ketosamine 6-phosphate 936 2-keto-3-deoxy- DL-manno-octosonate 12-ketoursodeoxycholic acid 1392 (KDO) 864 kievitone hydratase 471 2-keto-3-deoxy-manno-octosonate (KDO) – detoxifies kievitone 471 aldolase (KdoA) 872, 873 kinetic asymmetric transformation – natural substrates 873 (KAT) 328 2-keto-3-deoxy-6-phosphogalactonate kinetic resolutions (KDPGal) 864 – Chen equations, graphical representation 2-keto-3-deoxy-6-phosphogalactonate of 46 aldolase 173, 873–877, 973–977 – combined with Mitsunobu reaction 264 2-keto-3-deoxy-6-phosphogluconate – economic balance of 50 (KDPG) 864, 873, 874 – Evalue of 55 b-keto ester reductase (KER) 170 – general scheme of 47 2-keto glutarate, decarboxylation 930 – hydrolase-catalyzed 48 ketone, oxidative transformation of 1439 – intrinsic disadvantage of 1379 ketones – of rac acids/alcohols 262 – (R)-cyanohydrin 955 – of racemates 1613 – whole-cell catalyzed reductions of 33 – yield limitation of 50–58 ketones reduction Klebsiella oxytoca 1544 – asymmetric 34 kojibiose phosphorylase 1022 – based on substrate-coupled cofactor- Krebs cycle 920 regeneration with isopropanol 1054 ––use of isolated enzymes 1054–1058 l ––use of whole cells 1058–1063 Laccaria bicolor 1254 – based on wild-type microorganism and laccase 1548 glucose in a fermentation-like laccase-catalyzed coupling processes 1076–1079 – of tyramine via 4-O-5 bond 1823 – bulky, with two large substituents laccase-mediator system (LMS) 1338, 1344, 1085–1090 1346, 1352, 1361 – cofactor regeneration using chemocatalytic – Artificial regeneration systems 1352 and electrochemical methods – N-OH mediators 1362 1079, 1080 – oxidation of alcohols 1361, 1364, 1365 – enzyme-coupled cofactor-regeneration using – schematic representation of 1361 a formate dehydrogenase 1063 – with TEMPO 1362 ––use of isolated enzymes 1063–1066 – use of 1345 ––use of whole cells 1066–1068 laccases 1358–1363 – enzyme-coupled cofactor-regeneration using – oxidation mechanism of 1360 a glucose dehydrogenase 1068 lactaldehyde formation 937 ––use of isolated enzymes 1068–1070 b-lactam antibiotic ceftazidime 127 ––use of whole cells 1070–1073 lactamase 837 – enzyme-coupled cofactor-regeneration using b-lactamase 1758 a glucose-6-phosphate c-lactamase based processes 573 dehydrogenase 1074 b-lactam enantiomers 573 ––use of isolated enzymes 1074, 1075 – resolutions 574 ––use of whole cells 1074, 1076 lactate – enzyme-coupled cofactor-regeneration using – amperometric quantification of 1339 a phosphite dehydrogenase 1075, 1076 lactate dehydrogenase (LDH) 799, 1337 – reduction of keto esters 1095–1098 – direct electrochemical wiring of 1339 1966j Index

lactic acid L-tert-leucine – chemoenzymatic deracemization of 1390 – preparation of 1546 – electroenzymatic deracemization of 1390 leucine aminopeptidases 579, 587, 588 Lactobacillus brevis 1096, 1212, 1213, 1373 – active sites 589 Lactobacillus delbrueckii 786 – from bovine lens (blLAP) 589 Lactobacillus fermentum 1618 – peptide bond hydrolysis, reaction lactonase-catalyzed resolution mechanism 592 – yielding D-pantoic acid, flow scheme 507 leucine dehydrogenase catalyzed reductive lactones 300 amination 1183, 1186 – lipase-catalyzed ring-opening polymerization – L-amino acids with two stereogenic (ROP) 1810 centers 1190, 1191 – ring-opening polymerization (ROP) 1810 – L-b-hydroxyvaline 1188, 1189 lactoperoxidase 1557 – isotopically labeled L-amino acids 1189, L-ala-D/L-glu epimerase 1718 1190 L-alanine 781 – L-tert-leucine 1183–1186 L-alanine production 993 – L-neopentylglycine 1186–1188 L-amino acid oxidases (L-AAO) 1840 D-tert-leucine production L-amino acids – nitrile hydratase/D-amidase catalyzed – isotopically labeled 1189 cascade 604 – synthesis from a-keto acids by reductive Leu476Gln 174 amination 1188 N-levulinoyl D-mannosamine 872 – with two stereogenic centers 1190 Lewis acid 386 L-aminopeptidase 851 Lewis acid-based metal catalysis 1777 L-arabinose isomerase 1651 Lewis acid complexation 860 L-aspartame, enzymatic synthesis of 25 L-galactono-1,4-lactone dehydrogenase L-aspartase 749 (GALDH) 1342 L-aspartase-fumarase 750 L-glutamate 781, 1195 L-aspartase-fumarase superfamily L-glutamate dehydrogenase (L-GluDH) 1546 – biocatalytic scope and applications L-glutamic acid 781 752, 753 L-glyceraldehyde – catalytic mechanism 751, 752 – glycerol, GalOx-catalyzed oxidation of 1369 – diversity 752 L-histidine 749 – enzyme engineering 753, 754 L-homophenylalanine 779 – mechanism of aspartase reaction 751 L-6-hydroxy-norleucine 1194 – properties 750 libradyn, enzyme production – structure 751, 752 – contact information 1893 L-aspartate ammonia lyases 750 – enzyme products 1893 L-aspartate b-decarboxylase 848, 992 LibraGen, enzyme production 1893 L-aspartate ester – contact information 1894 – of chiral alcohol 154 – enzyme screening sets 1894 L-aspartic acid 781, 847 lichen macrolactone (þ)-aspicillin Lathyrus sativus 768 synthesis 894 L-b-hydroxyvaline 1188, 1189 life-cycle assessment (LCA) 1325 L929 cell death, induced by anti-DNA antibody ligand-interacting protein atoms 92 BV04-01 1754 ligase antibodies 1758, 1759 L-3,4-dihydroxyphenylalanine (L-DOPA) from ligases 10 catechol 997 light-driven cofactor recycling L-DOPA catalyzed by tyrosine phenol – concept of 1446 lyase 997, 998 lignin peroxidase 1559 L/D-tyrosinol 156 lignocellulose based materials, enzymatic Legionella pneumophila 769 modification 1819 Leishmania donovani 755 – esterases specific to lignocellulosic L-ephedrine 19 materials 1819, 1820 – microbial biotransformation 19 – glycosidases 1820 Index j1967

– glycosyltransferases 1820–1822 – production of 23 – oxidoreductases, coupling reactions L-methylaspartase 756 1822–1824 – biocatalytic application 758 – transesterification and transglycosylation – mechanism 757, 758 reactions 1819, 1820 – properties 756, 757 lignocellulose materials 1822 – structure 757, 758 limonene 1251 – substrate scope 758 (S)-limonene 1298 L-monosodium glutamate limonene enantiomers 1306 – conversion of 1547 limonene epoxidation 1300 L-neopentyl-glycine 1186 linear precursor, reductive amination 891 lobucavir, regioselective acylation of 310 linoleic acid 1245 lock-and-key 4 lipase long-chain dehydrogenases/reductases – from Bacillus subtilis (LipA) 159 (LDRs) 1040 – catalyzed enantioselective Lonza AG process, for production of polymerization 1809 (S)-piperazine-2-carboxylic acid 834 – catalyzed kinetic resolution 974 Lonza process, for selective oxidation – enantioselectivity, industrial hydrolysis of 2,5-dimethylpyrazine 1597 processes 505 LOX-pathway products 1245 – yielding (S)-ibuprofen, flow scheme 506 L-phenylalanine 25, 749 lipase-catalyzed resolution L-phenylalanine methyl ester 845 – reaction cascade 508 L-4-phenyl-3-amino-n-butanoic acid 779 – yielding enantiopure 2- L-phosphinothricin 796 methoxycyclohexanol, flow scheme 510 L-pipecolic acid – yielding (S)-hemisuccinate, flow – conversion of 1537 scheme 510 L-proline analogues lipase from P. aeruginosa (PAL) 161 – synthesis of 1544 lipase-mediated epoxidation 1290 L-rhamnose isomerase 1657–1660 lipases 251–255, 503–513, 1701, 1777 L-serine dehydratase 766 – Burkholderia cepacia lipase 259, 304 L-serine hydratases 767 – Candida antarctica lipase B 254, 261 L-sialic acid 172 – catalytic cycle of 253 LTB4 dehydrogenase 1150 – enantioselectivity of 259–261 L-tert-leucine 1183, 1186, 1219 – in esterifications 508–513 L-threo-3-methylaspartic acid 756 – in hydrolytic reactions 503–508 L-threonine 767, 768 – interfacial activation 254 L-threonine dehydratases 768 – lid, role of 254–256 L-to-D-peptide isomerase 1612 – Rhizomucor miehei lipase (RML) 334 L-tyrosine aminotransferase (TAT) 812 – rule of Kazlauskas 259 L-tyrosine decarboxylase (L-TyrDC) 60 – simulations of 102 luciferase 1413 – from Thermomyces lanuginosus 255 – light emission, mechanism 1413 Ò Lipitor , multistep process for lupus-associated cytopenia 1752 synthesis 1216 lyase/ligase reactions lipopolysaccharides (LPS) 448 – racemic resolution via 938–940 lipoxygenase-catalyzed allylic peroxidation lyases – mechanism of 1275 – enzyme catalysis reactions 9 lipoxygenases 1244, 1245, 1273 – miscellaneous lyases adding amines to C¼C liquid reactants 512 bonds 769–771 L-leucine dehydrogenase catalyses 1546 lymphoproliferative disorders 1748 L-lysine, conversion of 1537 lysine 1738, 1739 L-lysine oxidase 1536 – two-enzyme DKR process to 570 – use of 1536 lysine 2,3-aminomutase 1663, 1665 L-malic acid 992 b-lysine 5,6-aminomutase 1666 L-methionine 302 lysine cyclodeaminase 1536 1968j Index

lysine 6-dehydrogenase 1178 – with three stereogenic centers 297 lysosomal peptidases 689 meso compound 265 lysosomal storage disorders 1004 meso-diols, desymmetrization of 345 – primary cyclic meso-diols 345 m – tetrahydropyranyl diols 347 macrolide antibiotic amphotericin B – 1,3,5-triol derivative 346 – synthetic precursor 870 – using 1-ethoxyvinyl 2-furoate 346 macrolide antibiotic pentamycin 894 meso-2,5-hexanediol, desymmetrization macrophomate synthase (MPS) of 1379 – application 876 metagenome sequence tags(MSTs) 76 MAH metagenomics 90 – structure–function relationship 620 metagenome 72, 90, 390, 974, 1049, 1290 – substrate specificity 620 metagenomic sequences tags (MSTs) 72 major histocompatibility complex 690 metal-catalyzed hydrogenation malease 475, 476 – enzyme-catalyzed transamination 36 – enantioselectivity 475 metal-chelating compounds 612 – stability 475 metal ions 535 malic acid – substitution 591 – production from maleic anhydride 520 metalloenzymes 1553 malic acid production 517 metallohydrolases 1702, 1703 mammalian cytochrome P450 metallo monooxygenases 1236 monooxygenases 1274 – catalytic cycle 1235 mandelate pathway 619 metallopeptidases 683, 687 mandelate racemase 1633–1636 methane monooxygenases (MMOs) 1278, mandelic acid amide 612 1497 mandelonitrile stereoselective synthesis 953 – catalytic cycle 1235 mandelonitrile synthesis 947 (1S,2S)-2-methoxycyclohexanol 508 mannopentaose, transgalactosylation of 1821 p-methoxyphenyl (PMP) a-C-mannoside 883 – oxidative deprotection of 1548 mass spectrometry (MS) 121 (2R,3S)-3-(4-methoxyphenyl) glycidic acid medium-chain dehydrogenases/reductases methyl ester 506 (MDR) 1038, 1040, 1041, 1138–1142 – flow scheme 506 medium density fiberboards (MDFs) 1822 3-(4-methoxyphenyl)glycidic acid methyl ester MeHNL enzyme X-ray crystallography 969 hydrolysis 506 Meito Sangyo Co., Ltd, enzyme production 1-methoxy-2-propanone 850 – contact information 1895 N-methylamines, oxidation of 1547 – hydrolases 1895–1897 N-methyl-amino acid dehydrogenase Meldola’s blue 1344 1196–1199 membrane-bound hydroxylases 1270 methylaspartate ammonia lyases 757, 758 membrane-bound peptidases 689 – reactions catalyzed by 758 MenD 926 N-methylcarbamate hydrolyzing enzymes 567 – physiological donor 926 3-methyl catechol 1497 MenD-catalyzed physiological/non- methyl-chymotrypsin (MeCT) 710 physiological transformations 927 4-O-methyl-D-glucuronic acid Merck’s HIV-1 protease inhibitor Indinivir – of glucuronoxylan and lignin alcohols 1820 Sulfate 1511 L-a-methyl-3,4-dihydroxyphenylalanine meso-a,e-diaminopimelate (L-a-methylDOPA) 575 D-dehydrogenase 1179 3,4- methylenedioxyacetophenone 1209 meso-carboxylates, enantioselective (S)-(3,4-methylenedioxyphenyl)-2- hydrolysis 292, 296–298 propanol 1210, 1211 – alternative enantioselective route to – scheme forproduction using 1210 oseltamivir phosphate 298 1-methyl-1,2-epoxycyclohexane 405 – products from enzymatic 2-methylglutaronitrile 824 desymmetrization 292 methyl group oxidation 1497 Index j1969 methyl halides, enzymatic formation of – properties 609, 610 1575 microbial D-selective a-H-a-amino acid amide N-methylhydantoin amidohydrolase 657 hydrolases 2-methylindole, treatment of – properties 596–599 – with horseradish peroxidase (HRP) 1550 microbiology, history 18 N-methyl- L-amino acid 1197 Micrococcus luteus N-methyl- L-amino acid dehydrogenase – PAN fibers, degradation of 1817 (NMAADH) 1536 microperoxidase 1554, 1559 N-methyl- L-phenylalanine 1196 miglitol, synthesis of key intermediate for 1593 Methylobacterium capsulatus 1285 mineralocorticoid aldosterone 1255 methyl phenyl sulfide (thioanisole) 1553 MIO enzymes 759 5-methylpyrazine-2-carboxylic acid 1596 – ammonia lyase, proposed mechanism 759 N-methylpyrrolidine, deracemization – tyrosine aminomutase 1669 of 1543 – unified mechanism for 1669–1671 a-methyl-substituted amino acid amides miscellaneous lyases adding amines to C¼C 607 bonds 769–771 methyl t-butyl ether (MTBE) 834, 928, 980 Mitsunobu reaction 264, 1391 2-methyltetrahydrofuran (2-MTHF) 928 M17 leucine aminopeptidases (LAPs) 579 DL-a-methyl valine amide – high-resolution structure 591 – hydrolysis 608 molecular dioxygen, activation of 1228, 1229 Met365Leu/Leu461Ser 174 molecular dynamics (MD) simulations 98, 628 (S)-metoprolol 1587 molecular imprints 1735 metoprolol, synthetic route to 1282 molecular sieve 606 micelles 708 molybdenum hydroxylases 1239 Michael addition, of water 468, 481, 483 monoamine oxidase (MAO) 779, 781 Michaelis complexes 44, 681 – from Aspergillus niger 167, 1840 Michaelis–Menten kinetics 43, 44, 220, 221, – desymmetrization of 1544 603, 1763 – substrate specificity of 1542 Michaelis and Menten 4 mono-aromatic compounds, biodegradation microbial biotransformations of 1489 – application of 19 monoclonal anti-DNA antibodies 1751 – with wild-type strains 18, 19 monoclonal 24B11 antibody 1739 microbial deoxysugar phosphate mono(2-hydroxyethyl) terephthalate – natural substrates 881 (MHET) 1813 microbial enzymes 194, 195 mononuclear non-heme iron enzymes 1270 – catalyzing 26 mononuclear non-heme iron – extraction of 197 oxygenases 1302 microbial epoxide hydrolases. See epoxide monooxygenases 1410, 1553, 1555, 1558, hydrolases 1817 microbial hydantoin metabolism, application – enzyme 1285 to biotechnology 651–656 – oxidation of 2-methylquinoxaline by microbial nitrilase 1596 – catalytic mechanism 548 – oxidation of sulfides by 1554 – crystal structure 548 – types of 1496 microbial nucleic acid, overview 665 monooxygenation reaction 1307 microbial b-peptidyl aminopeptidase monophosphate esters 1003 (b-aminopeptidases) monosaccharides synthesis 882 – properties 615–617 monosodium glutamate (MSG) 1546 microbial P450 monooxygenases 1274 – enzymatic oxidation of 1546 microbial L-selective a-H-a-amino acid amide – monosodium L-glutamate 575 hydrolases mono-substituted a-/b-amino acids – properties 584, 585 – structures 613 microbial L-selective a-alkyl-a-amino acid DL-5-monosubstituted hydantoin 656 amide hydrolases 5-monosubstituted hydantoins 1970j Index

– ATP-dependent hydrolysis 657 NAD(P)-independent dehydrogenases DL-5-monosubstituted hydantoins 651 1341–1345 monoterpenes a-pinene – regeneration of 1344, 1345 þ – monooxygenation of 1299 NAD(P) regeneration approaches 1336 monoterpenoid indole alkaloids 770 – aldehyde dehydrogenases 1408 Monte Carlo simulation model 153 – enzyme-coupled regeneration 1337 Morganella morganii 30 – one- and two-electron mediators 1340 Morita–Baylis–Hillman reaction 1717 – photochemical methods 1340 Mortierella isabellina 1557 Nagase ChemteX Corporation, enzyme moxalactamase activity 29 production 1897 muconate-lactonizing enzyme 1718 – contact information 1898 cis,cis-Muconic acid 1518 – hydrolases 1898, 1899 Mugil cephalus 401 nanomachines 105 multi-chiral amino acids naphthalene dioxygenase (NDO) 894, 1252, – simultaneous resolution 663 1303, 1304, 1495, 1508, 1557 multicopper oxidases 79 – electron-transfer process and catalytic cycle multi-enzyme conversion 219 of 1495 multifunctional enzyme type 1 (MFE-1) 489 narcotics 1737 multi-ketone substrates native chemical ligation, principle of 695 – kinetic resolutions on 1468 native strains 537 multiple reactors – disadvantages 540 – configurations 224 natural aldolase enzymes 908 – use of 223 natural cis-dihydrodiols 1514 multistep 16, 35, 37, 81, 1216 naturally occurring antibodies with amidase multiple sclerosis 1748 activity 1759, 1760 multistep bioconversions 81 naturally occurring antibodies with nuclease multistep synthetic process activity 1747–1754 – screening system for 81 natural strains, disadvantages 540 mutagenesis 1556 NDT degeneracy, library coverage mutases 1661–1671, 1688 calculated 133 – syntheses using 1688 negative stain electron microscopy, mutations 1719 combination 546 Mutazyme polymerase 123 nerve toxins 1748 Mycobacterium M156 1281 Neu5Ac aldolase 172 Mycobacterium tuberculosis 391, 1178, 1556 NeuNAc synthetase (EC 4.1.3.19) 864–872 mycophenolic (MPA) acid neuraminic acid derivatives 868 – acyl-glucuronide production 515 Neurospora crassa 1209 – enzymatic glucuronidation 515 Newton’s second law of motion 97 myoglobin 1554, 1557 N-hydroxy-N-methylamines, oxidation myristyl myristate 351 of 1547 niacin 1590, 1591 n Nicotiana tabacum 1142 NADH:ferredoxin oxidoreductase 1275 nicotinamide-dependent dehydrogenases NADH-rubredoxin reductase 1280 catalyze 1535 NAD(P)-dependent alcohol nicotinamide industrial-scale production 536 dehydrogenases 1341 nicotinamide synthesis 524 NAD(P)-dependent sugar alcohol nikkomycin antibiotics 874 dehydrogenases 1343 – amino acid, stereoselective synthesis 875 NAD(P)H-dependent flavoenzymes 1554 – biosynthesis 878 NADPH-dependent glycerol dehydrogenase nikkomycins 1192 (Gox1615) from Gluconobacter nitric oxide (NO) 535 oxydans 1048, 1049 nitrilase 824 NADPH-dependent N-methyl-L-amino acid – catalytic mechanism 549 dehydrogenase 1199 – characteristics 550 Index j1971

– classification 550 nitrobenzene dioxygenase (NBDO) 1508 – diversity 557 5-nitrobenzisoxazole 1722 nitrilase-containing biocatalysts 554–557 nitrobutanal 887 – enzyme preparations 555, 556 nitrogen-containing compounds, utilization 538 – whole cell biocatalysts 554, 555 nitrogen-containing organic compounds 821 nitrilases 37, 545–554 1-nitronaphthalene, NBDO oxidation 1509 – aliphatic nitrilases 546 4-nitrophenyl-4,6-O-ethyliden-a-D- – aromatic nitrilases 546 maltogeptazyde 1767 – characteristics 547 Nitto Chemical Industry, – dinitriles, regioselectivity/ biotransformation 523 monohydrolysis 550, 551 NNK – enantioselectivity 552–554 – library coverage calculated for 133 – (E)-/(Z)-selectivity 551, 552 – NDT codon 144 – occurrence and classification 546 – randomization 167 – protein structure and oligomerization – vs. NDT systems 132 546–548 Nocardia farcinica 1815 – reaction mechanism 548 Nocardioides simplex 3E 1503 – side activities 548–550 non-catalytic proteins 1717 – substrate specificity 550 non-enzymatic chemical methods 936 nitrile, direct interaction 536 non-enzymatic reaction 977 nitrile hydratase 28, 523, 822, 823 non-heme iron 1572, 1578, 1712, 1713 – biocatalysts containing, whole-cell – reaction mechanism 1575 biocatalysts 537–542 non-heme metallo monooxygenases 1235 nitrile hydratase enzyme (NHases) 61, – CH bond oxyfunctionalizations catalyzed 533–537 by 1237 – catalyzed processes 542 – dopamine b-monooxygenase 1236 – characteristics 539 – hydroxylation of nicotinate 1240 – crystal structures 534 – hydroxylation of phenylalanine 1238 – discovery 533 – non-heme diiron monooxygenases 1235, – enantioselectivity 536, 537 1236 – formation 538, 541 – peptidylglycine a-amidating monooxygenase – heterologous expression 541 (PAM) 1236, 1239 – isolation 534 – peptidylglycinea- – metal center, structure 535 hydroxylatingmonooxygenase – molecular screening 534 (PHM) 1236, 1239 – occurrence and classification 533, 534 – tetrahydropterin-dependent – protein structure, metal cofactors, and monooxygenases 1236 posttranslational modifications 534, 535 non-natural aldol donors, utilization 862 – reaction mechanism 535, 536 non-natural sugar derivatives, production – substrate specificity 536 of 1657 – types 540 nonphosphorylated (NAD) nitrile-manipulating enzymes 1900 – coenzyme 1409 nitriles hydrolysis – cofactor 1338 – to amides 533–542 non-polarizable force fields 104 – biocatalysts containing nitrile non-proteinogenic amino acid piperazine-2- hydratase 537–542 carboxylicacid 581 – to carboxylic acids 545–557 non-proteinogenic L-a-amino acids 1187 – nitrilase-containing biocatalysts 554–557 non-ribosomal peptide synthesizing (NRPS) – nitrilases 545–554 mechanism 1612 – nitrile hydratases 533–537 non-steroidal anti-inflammatory drugs nitrile-utilizing microorganisms 533 (NSAIDs) 335, 567 nitroaldol reaction, asymmetric (þ)-nootkatone, isolated yields 1309, 1310 – enzyme promiscuity in 38 norsesquiterpene 5,6- nitroalkenes 1149, 1150 dehydrosenedigitalene 307 1972j Index

Northern blot analysis 538 organic–aqueous biphasic system 979 N-PMP (p-methoxyphenyl) protecting group organic cyanides, hydrolysis 545 – removal of 1548 organic solvents 978 NSC Technologies process, for production organocatalysis 473, 857 D-amino acids 849 organocatalytic transformations thiamine nuclear magnetic resonance (NMR) 67 diphosphate (ThDP)-dependent enzymatic – analysis 930 transformations – tomography 866 – development 919 nucleophile, structure 885 organolithium compounds 1004 nucleophilic donor component 859 organo-nitrogen-containing compound 474 nucleophilic halogenation 1575 organophosphate hydrolase (OPH) 1893 nucleophilic peroxyanion facilitates organophosphorous poisons (OPPs) 1747 Baeyer–Villiger reactions 1441 organophosphorus covalent inhibitors 1748 Nzomics Biocatalysis, enzyme ornithine 4,5-aminomutase 1666 production 1899, 1900 Osaka SaikinKenkyusho, enzyme – carbohydrate hydrolyzing and modifying production 1904 enzymes 1902–1904 – hydrolases 1904 – contact information 1900 oseltamivir phosphate 298 – nitrilases 1901, 1902 oversampling factor – nitrile hydratases (NHase) 1900, 1901 – library coverage, correlation 131 oxaloacetate decarboxylase (ODC) 795 o oxaloacetic acid 781 O. anthropi amidase-catalyzed resolution oxidation reaction 611 – of alkanes 1248–1250 1,7-octadiene, epoxidation of 1280 – of N-butylglucamine 1592 – O2-dependent halogenases 1572, 1578 by dehydrogenases 1591 – reaction mechanism 1575 – by dioxygenases 1598–1603 old yellow enzyme (OYE) 6, 1116 – fatty acids 1246–1248 – enone reductions 1118 – of cis-b-methylstyrene 1717 – OYE2 gene 1121, 1148 – by monooxygenases 1594–1598 oleate hydratase 469 – by oxidases 1586 – catalyzed synthesis of whiskey flavor 469 – processes using biocatalysts 1585, 1586 olefinic aliphatic and araliphatic acyloins – of N-protected 1-amino-L-sorbitol 1593 929, 930 – steroids 1255–1258 olefinic monoterpenes, microbial epoxidations – at sulfur 1553 of 1298 oxidation of amino groups 1559–1561, 1560 olefins – by Fe-dependent enzyme 1560, 1561 – epoxidation 1283–1284, 1289 – by Mn-containing, radical-mediated, – production 1407 hydrogen peroxide-dependent oligomeric protein complexes 909 enzyme 1561, 1562 oligophosphate esters 1004 oxidation of sulfides 1554–1557 oligosaccharides 417, 442 – by monooxygenases and by whole olive oil 191 organisms 1554–1557 D-olivose – by peroxidases and haloperoxidases – FruA-catalyzed preparation 885 1557–1559 one-pot single-step process 62 oxidation of terpenes and terpenoids 1250, open reading frames 662 1251 operating window 238 – dicyclic monoterpenes 1252, 1253 opine dehydrogenase 1199 – monocyclic monoterpenes 1251, 1252 optically enriched cyanohydrins, lipase- – sesquiterpenoid analogs 1254, 1255 catalyzed formation 973 – sesquiterpenoides 1253, 1254 optically pure cyanohydrins, follow-up oxidation–reduction deracemization reactions 976 process 1541 organic acids 545 oxidation–reduction sequence 52 Index j1973 oxidative biotransformation, of sulfides 1553 – biocatalyzed 50 oxidative cofactor 12 – chemodivergent 48, 49 oxidative deamination – enzymatic, quantification of 49 – catalyzed by immobilized D-amino acid – general scheme of 49 oxidase 1586, 1587 – regiodivergent 49 oxidative degradation – stereodivergent enzymatic 49 – of porphyrin ring 1553 parameter estimation 239, 240 oxidative enzymes 1586 – kinetic model 239 oxidative pyrimidine metabolism 665 – rate equation 239 oxidative sulfitolysis 842 P450 BM-3 mutants oxidized nicotinamide cofactors – oxidation products 1302 – electrochemical regeneration of 1339 P450cam 1414 oxido-reductase antibodies 1765, 1766 P450-catalyzed epoxidations 1275 oxidoreductases (EC 1) 6, 1206–1208, 1326 p-cresol methylhydroxylase (PCMH) 1344 – enzyme catalysis reactions 7 – electrochemical regeneration of 1344 oxidosqualene cyclase 1719 PEG-modified enzymes 709 oxime resin 725 pelitrexol 282 oxiranemethanols 311 penicillin acylase 828, 830, 838 oxirane ring, formation and opening penicillinase 219 1755, 1756 penicillin G acylase 23 2-oxo acid dependent iron enzymes 1272 penicillin-recognizing proteins 600 oxo-acid lyases, syntheses using 995–997 Penicillium citrinum 158, 170 oxobicyclononans 1739 pentose phosphate pathway 920 2-oxobutanoate 767 P450 enzymes 1713 2-oxobutanoic acid 877 PepA hexamer 593 2-oxoglutarate-dependent enzymes 1712, peptidase-catalyzed peptide synthesis, 1713 Influence of reaction medium 707 2-oxo-hept-3-ene-1,7-dioic acid hydratase peptidases 675, 680 (HpcG) 480, 481 – classification, principles of 684 2-oxopent-4-dienoate hydratase – EC classification 684 (2-hydroxypentadienoic acid hydratase) – evolutionary classification, into families (OEH) 482 and 685 15-oxoprostaglandin reductase (PGR) 1138 – families and clans 684–688 2-oxo-3-sulfinopropanoic acid 793 – inhibitors 690, 691 oxyfunctionalization of CH bonds 1245, – manipulations to suppress competitive 1246 reactions 706 oxygenases 1227 – medium engineering by reducing water oxygenated pyrrolizidine alkaloids, synthetic content 710–714 routes 891 – medium engineering with organic oxygen-containing fused cyclobutanone 1473 solvents 706–710 oxygen-derived heme-iron bound – modification of artificial substance P hydroperoxide 1414 precursor protein 735 oxynitrilases 948, 1719. See also Syncore – specificity 678 hydroxynitrile lyase enzymes – substrate engineering 714, 715 – types, based on catalytic mechanisms 680 p peptide amidases (R)-PAC synthesis 925 – activity 622 PaHNL catalyzed cyanohydrin reaction 967 – cleavage reaction catalyzed by 623 pancratistatin – from Flavedo of Oranges 622–626 – enzyme-catalyzed asymmetric – from microbial sources 626–628 synthesis 895 – properties 623 pancreatic peptidases 676 peptide-based antibiotics 779 Paracoccus seriniphilus 769 peptide bond, approaches to irreversible parallel kinetic resolutions (PKRs) 45, 48 formation of 715 1974j Index

– anionic substrate mimetics 721–723 phenolics – cationic substrate mimetics 720, 721 – covalent enzymatic attachment 1824 – chemoenzymatic substrate mimetic – substrates 1358 approach 725, 726 phenothiazine derivatives 1346 – highly activated acyl donors 726–729 phenoxyacetone 1216 – hydrophobic substrate mimetics 723–725 3-phenoxybenzaldehyde, – irreversible C–N ligations 717 (S)-cyanohydrin 955 – mechanism of substrate mimetic phenylacetone monooxygenase (PAMO) 168 hydrolysis 717–720 – crystallographic structure – use of nonpeptidases 715 determination 1442 – use of proteolytically inactive – protein crystal of 1443 zymogens 715, 716 (R)-phenylacetylcarbinol 992 peptide-cleaving enzymes 676–680 phenylacetylcarbinol (PAC) 991 peptide dendrimers, construction 909 – derivatives formation 926 peptide hydrolysis 588 – fermentative production 924 peptides 675 phenylalanine 1238 – approaches, preference of 705, 706 D-phenylalanine amide 601 – C-terminal amidation 626 phenylalanine aminomutase (PAM) 626, 763 – enzymatic modification 737, 738 – availability 627 – enzymatic synthesis, principles of 698, 699 – catalysis mechanisms 628 – equilibrium-controlled synthesis 700, 701 phenylalanine ammonia lyase 758 – general manipulations in favoring phenylalanine dehydrogenase 1193 synthesis 699, 700 phenylalanine dehydrogenase catalyzed – kinetically controlled synthesis 701, 702 reductive amination 1191 – prediction of synthesis by S0 subsite – synthesis of allysine ethylene acetal 1192 mapping 702–704 – synthesis of (S)-2-amino-4-phenylbutanoic – synthesis, tools for 692–697 acid 1191, 1192 – in vitro synthesis 622 – synthesis of (S)-3- b-peptides, features 613 hydroxyadamantylglycine 1193, 1194 peptides hydrolysis 676 – synthesis of N-terminal amino acid portion of – mechanism for 679 nikkomycins 1192, 1193 Peptostreptococcus asaccharolyticus 769 phenylalanine hydroxylase 1238 perhydrolases 1576, 1700 phenylalanine racemase 1612 perillyl alcohol 316 phenylalanine residue 1314 peroxidases 1233, 1277, 1354–1358, 1553, phenylalkenes cleaved, by trametes hirsuta 1554, 1555, 1719 FCC 047 1313 peroxidases catalyze 1287 2-phenylethanol 1595 peroxidases from horseradish (HRP) 1357 1-phenylethylamine 792 peroxidases from soybean (SBP) 1357 – enantioselective amidation of 1838 peroxyanion 1440 (R)-phenylethylmethoxyamide 1837 peroxycarboxylic acid 1700 D-phenylglycine (D-Phg) 575 peroxyflavin/hydroperoxyflavin 1277 phenylmethanesulfonyl fluoride pesticides 1737 (PMSF) 600, 691 PET-hydrolases 1812 phenylmethylsulfonyl fluoride 680 Pfizer’s neuropathic 1-phenyl-n-propylamine (PPA) 811 – active pharmaceutical ingredient (API) phenylpropanoid synthesis 761 of 35 rac-2-phenylpropionamide, (S)-stereoselective Phanerochaete chrysosporium 1559 amidase resolution 567 pharmacologically active compounds, 3-phenylpropionate 1137 composed of non-natural amino acids/ 2-phenylpyrrolidine, chemoenzymatic amines 780 deracemization of 1840 Phaseolus radiatus 405 phenylpyruvate decarboxylase (PPDC) 929 1,10-phenanthroline 680 phenylpyruvate decarboxylase from phenol hydroxylases 1497 Azospirillum brasiliense (PPDC) 922 Index j1975 phenylserine dehydratase 766 2-piperazinecarboxamide resolution 569 phenylserine derivative 904 piperidine-2-carboxamide, amidase catalyzed Phizicky concept of screening 153 resolution reactions 582 phosphatases 503, 1003, 1006, 1009, 1010 piperidine-2-carboxyamide 586 phosphate donor 1004 a-N-pivaloyl-tert-leucinamide 1184 phosphate esters 1003, 1004 plant enzymes 195, 196 – containing compounds 1003 – extraction of 198 – hydrolysis 1747 Pleurotus osteatus 1022 phosphate group, ionic nature of 1003 Pleurotus sapidus 1253 phosphate hydrolyzing enzymes 1009, 1010 P450 monooxygenases 170, 1278, 1287, 1547 phosphate monoester 1011 – aldehydes catalyzed, decarboxylations phosphate transfer reactions of 1416 – enzymes used in 1005 – analysis of 93 phosphite dehydrogenase (PTDH) 1444 pneumonia 1418 phosphocreatine 1006 p-nitrophenyl-b-D-fucopyranoside phosphocysteine 1010 (pNP-fuc) 143 3-phospho-D-glycerate 1025 p-nitrophenyl phosphorylcholine 1741 phosphodiester bond 1748 polarimetry 232 phosphodiesterolytic antibodies 1752 polyacrylic acid phosphoenolpyruvate (PEP) 864, 1006 – NMR analysis of 1816 – neuraminic acid synthetase (NeuS) 871 polyacrylonitrile (PAN) fibers 1815, 1817 phosphoenolpyruvate carboxylase poly(alkylene terephthalate)s (PATs) 1808, (PEPC) 1868 1811 phosphoglucomutase 1021 – enzymatic hydrolysis of 1812, 1814 6-phosphogluconate dehydratase 478 poly(butylene succinate), enzymatic synthesis phosphohydrolases. See phosphatases of 1809 N-(phosphonomethyl)glycine 1366 poly(1,4-butyl sebacate) 1809 – chemoenzymatic synthesis of 1366 polychlorinated biphenyls (PCBs) 482 phosphorochloridates 1004 polyesters, enzymatic synthesis of 1807 phosphorus load in environment 1010 poly(ethylene terephthalate) (PET) 1811 phosphorylases 1021, 1022 – PVC-coating of 1814 phosphorylated intermediates 1007 – surface morphology 1813 v-phosphorylated ketose 898 polyglycerol-3-esters 512 phosphorylating potential 1005 polyglycerol-3 laurate 351 phosphorylation polyhydroxy compounds 1004 – enzymes used in 1005 polyketide syntheses, assembly lines 1444 – of free hydroxyl group of drug 1003 polymerase chain reaction (PCR) 27, 119 – by kinases 1007 – based saturation mutagenesis 130 phosphoryl chloride (POCl3) 1004 – mutagenic libraries 150 N-phosphoryl oxazolidinones 1004 – screening protocols, application 534 phosphotransferase 1011 polymerase-chain-reaction-amplified DNA pH profile 74 probe 657 phylogenetic analysis 1449 polymerization 823 phytase 1010 poly(methyl methacrylate) (PMMA) 513 Pichia anomala 1098 polyols, regioselective oxidation 1334, Pichia pastoris 993, 1363 1373–1378 picolinic acid 826 polyphosphates 1006 Pictet–Spengler reaction 770 polysaccharide phosphorylases 1021 pinene 1252 polysaccharides 191, 213 (RS)-piperazine-2-tert-butylcarboxamide poly(styrene-co-4-vinylbenzyl alcohol) 1818 – resolution 583 poly(trimethylene terephthalate) (PTT ) 1814 piperazine-2-tert-butylcarboxamide 614 porcine liver esterase (PLE) 213 piperazine-2-carboxamide – catalyzed desymmetrizations of – amidase catalyzed resolution reactions 582 malonates 294 1976j Index

porcine pancreas lipase (PPL) 251 – enzymatic enantioselective synthesis of a P. putida leucine aminopeptidase (ppLAP) chiral sulfoxide 296 – X-ray structure 590 – synthesis of (þ)-peloruside A 295 PQQ-catalyzed oxidation mechanism 1342 prochiral ketones precipitation 211 – Baeyer-Villiger oxidation of 51 – by changing pH 212 – reduction of 51 – by organic solvents 212 prochiral selectivity 51 – by salting out 211, 212 prodigiosin biosynthetic pathway 934 – by water-soluble polymer 212 prodrugs, phosphate- containing 1003 pregabalin, second-generation multistep product diversity 882–895 route 35 product enantiomers, accessment 1150 prnD gene 1560 – using mutant enzymes 1152, 1153 process engineering 15, 22, 217–242, – using wild-type enzymes 1150–1152 1292, 1315 product recovery process intensification 236 – from biocatalytic reaction 229 – environmental assessment tools 237 – downstream processing and 229, 230 – enzyme immobilization 234 profens 335 – intensification methods 234 prokaryotic monooxygenases 1516 – LCA methodology 237 proline 4-hydroxylase 1243 – operating windows 238 proline racemase 1618, 1626–1628 – organic solvents, use of 235 – reaction mechanism 1627 – parameter estimation 239, 240 propanediol 332 – process metrics required for an effective 2-(prop-1-enyl)thiophene 1313 process 232, 233 2-propio-2-hydroxybutyrate 930 – process simulation 236, 237 propionate 768 – resins, use of 235 propylene 1,2-dinitrate 1119 – sensitivity and uncertainty analysis 238, 239 propylene, oxidation of 1285 – in situ product removal 235 10-(3-propylsulfonate)phenoxazine (PSPX) 1362 process operation 231 proteases – control of operating parameters 231 – Achromobacter lyticus protease 706 – reaction control 231, 232 – degradation 213 process simulation 263, 237 – inhibitors 213 prochiral and meso-carboxylates via proteasome 690 transesterification N-Cbz-protected amino aldehydes 889 – alcoholysis of protein-based materials, enzymatic –– dibenzoates 338 modification –– glutaric acid anhydrides 339 – crosslinking and grafting 1824, 1825 – desymmetrization of 237–239 – hydrolytic surface modification 1824 –– 3-substituted glutaric acids 338, 339 protein-bound water molecules 101 prochiral and meso-diols, enantioselective protein complexity 1520 formation of carboxylates from 339 protein database 73, 587, 603 – desymmetrization of protein design 31, 94, 95, 102, 107, 149, –– 2,2-disubstituted 1,3-diols 342–344 803, 851 –– prochiral diols 339, 340 protein, de novo design 103 –– 2-substituted 1,3-diols 340–342 protein dynamics 106 –– 1,3,5-triol derivatives 344, 345 protein engineering 28, 94, 140, prochiral carboxylates, hydrolysis 292–296 145, 152, 167, 784, 801, 802 – cosolvent effects 294 – to add new catalytic steps 1717, 1718 – enantioselective synthesis of axially chiral, – to convert 3,4-dihydrodiols into 1515 tetra-ortho-substituted – for decreasing substrate and product biphenylderivatives 295 inhibition 804, 805 – enzymatic desymmetrization – goal of 94 –– of prochiral malonates 293 – of hydantoin-transforming enzymes –– products from 292 663–665 Index j1977

– and improvement of catalytic – based protein production system 572 performance 365 ––advantage 572 – to increase affinity of P2O towards 1352 Pseudomonas oleovorans 1279, 1556 – for increasing activity and Pseudomonas putida 759, 793, 1281, thermostability 803, 804 1294, 1417 – methodologies 15, 26–31 – ATCC3315 1416 protein family, biochemical functions of 91 Pseudomonas solanacearum 836 protein flexibility 100 Pseudomonas sp. 1292, 1815 – in organic solvents 101 – NCIB 9816-4 1495 protein function, UniProt 69 – strain CF600 1496 protein isolation 1443 Pseudomonas testosteroni 1094 protein kinase 1766 purification of enzymes 199 proteinogenic amino acids 583 – affinity chromatography 209–211 protein phosphatases 1010 – gel filtration (GF) 207 protein purification experiments 587 – hydrogen bond chromatography 208, 209 proteins – hydrophobic interaction – acetamidase/formamidase family 612 chromatography 203–206 – catalytic function 908 – ion-exchange chromatography 199–203 – evolution of 119 – reversed-phase chromatography 207, 208 – high-resolution structure of 90 – salting-out chromatography 211 protein scaffolds 909 – stabilization during 213 protein sequence–activity relationships putidaredoxin reductase 1258 (ProSARs) pyanose-2-oxidase (P2O) 1352 – analysis of 150 – stereoinversions catalyzed 1405, 1406 – formal representation of 150 – substrates, selection 1353 – procedure 151 Pycnoporus sanguineus 1557 protein sequences 69, 74 pyrazine-2-carboxamide 834 protein–solvent system, dynamics of 101 2,3-pyridinedicarboxyimide protein splicing 696 – hydrolysis 668 protein structure, stabilization of 100 pyridoxal-dependent enzymes 1705–1707 protein systems, simulation of 104 pyridoxal phosphate (PLP) 784 proteolysis 679 – dependent enzymes 765 – importance of 688–692 – reactions catalyzed by 766 – of proteins for sequence analysis and 691 pyridoxal 50-phosphate enzymes 482 proteolytic enzyme 675 pyrimidine bases, reductive degradation Proteus myxofaciens 1618 651 protocatechuate 2,3-dioxygenase pyrimidine degradation pathways 669 (PC23DO) 1504 pyrophosphate (PPi) 1006 protocatechuate 3,4-dioxygenase pyrroline-2-carboxylic acid 1197 (PC34DO) 1503 pyruvate protocatechuate 4,5-dioxygenase – decarboxylation 935 (PC45DO) 1504 – non-oxidative decarboxylation 932 proton donors/acceptors 924 pyruvate decarboxylase (PDC) 800, 866 protozoan parasites 580 – enzymatic promiscuity 920 Prunus amygdalus 993 – ligation products 925 Pseudomonas aeruginosa (PAL) 145, 284, 1279 pyruvate dehydrogenase (PDH) 937 – binding pocket of 146 pyruvate kinase 1025 – lipase 974 pyruvate oxidase (PyOx) 1420 – X-ray structure 145 – decarboxylative phosphorylation of Pseudomonas cepacia 297 pyruvate 1419 Pseudomonas chlororaphis 20 pyruvate/phosphoenolpyruvate-utilizing Pseudomonas dacunhae 848, 992 aldolases 864–877 Pseudomonas fluorescens 311, 312, 752, 768, – N-acetylneuraminate (NeuNAc) 931, 1250 aldolase 864–872 1978j Index

– 3-deoxy-D-manno-2-octulosonate (Kdo) – TK-catalyzed reaction 939 aldolase 872, 873 racemic a-hydroxyaldehydes – 4-hydroxy-3-methyl-2-keto-pentanoate – resolution 881 aldolase (HkpA) 877 racemic 3-hydroxybutanal 884 – 2-keto-3-deoxy-6-phosphogluconate (KDPG) racemic ketones, classical kinetic resolution aldolase 873–877, 973–977 of 1456 – SanM 877 racemic linear cycloketones – kinetic resolution of 1460 q racemic linear ketone substrates quantitative structure-activity relationships – conventional kinetic resolution of 1460 (QSARs) 150 racemic 2-methyl-2- – analyses 91 hydroxyhexanenitrile 966 – approaches 91 racemic mixtures, kinetic resolution (KR) 45 quantum chemical analysis 99 racemic 1-naphthylglycine amide, QuikChange protocol 129 resolution 611 – schematic illustration of 129 racemic N-methylpyrrolidine 1543 quinohemoprotein dehydrogenases (QH- racemic O-methyl-N-hydroxyamines, ADH) enantioselective kinetic resolution 1543 – quinoid-based oxidation mechanism racemic piperazine-2-carboxamide 582 of 1341 racemic primary amines, dual transaminase/ quinoxaline-2-carboxylic acid amino acid oxidase 1539 – synthesis of 1416 racemic 3,3,3-trifluoro-2-hydroxy-2- quinuclidine ester 288 methylpropionamide 618 – hydrolysis 613 r racemization 262, 845 rac-benzoin – biocatalytic, hydroxy compounds using – BAL-catalyzed kinetic resolution 939 microbial cells 1637 racemases 1609, 1715, 1716, 1893 – at hydroxy-substituted carbons 1632, 1633 – syntheses using 1685–1687 racemizations 1379–1385, 1610 racemates resolution 973–975 rac-primary alcohol ester 261 – esterase/lipase as catalyst 973–975 – enantioselective hydrolysis 261 – hydroxynitrile lyase as catalyst 973 Ralstonia pickettii PKO1 1498 racemic acetate random chimeragenesis on transient templates – enantioselective hydrolysis 974 (RACHITT) 137 racemic amines random drift mutagenesis (RNDM) 137 – kinetic resolution of 1837 random insertional–deletional strand racemic b3-amino acid amides exchange (RAISE) mutagenesis 127 – b-aminopeptidase catalyzed kinetic – schematic diagram of 128 resolution 614 random insertion and deletion (RID) 124 racemic a-substituted cycloketones – mutagenesis 127 – kinetic resolution of 1458, 1459 random strand transfer recombination racemic 2-azidophenylacetic acid amide 621 (RSTR) 137 racemic N-t-boc piperazine-2-carboxamide rapid freeze quenching techniques 968 – L-leucine aminopeptidase (LAP) catalyzed raspberry ketone 1113 resolution 581 Rauvolfia serpentina 770 racemic 4-chlorophenylalanine (R)-[3,5-bis(trifluoromethyl)phenyl] – oxidation of 1546 ethan-1-ol (6) racemic cyanohydrins – production of 1838 – enantioselective HNL-catalyzed reaction control 231, 232 decomposition 973 reaction engineering, role of 218, 219 racemic cycloketone substrates reactive oxygen species (ROS) 1345 – conventional kinetic resolution of 1457 reactor, options and characteristics 219, 220 racemic 2,3-diaminopropionic acid 1537 reactor scale-up 228, 229 racemic 2-hydroxy aldehydes reactor selection criteria 233 Index j1979 reactors for soluble enzymes 225–227 Rhodococcus erythropolis 391, 405, 1210, 1215, reactors for use with multiphasic 1306, 1557, 1587 systems 227, 228 Rhodococcus opacus 1252 recombinant DNA technologies Rhodococcus rhodochrous 20, 28 – advantages 579 – B-276 1282 recombinant DNA technology 217, 625, 694, Rhodococcus spp. 1519 735, 841 Rhodococcus strains 533 recombinant E. coli based system 587 Rhodotorula glutinis 398, 406, 762 recombinant E. coli biocatalyst 588 Rhodotorula gracillus D-amino acid recombinant expression system 554 oxidase 1538 recombinant NADH-dependent opine (R)-2-hydroxy-4-phenylbutyric acid 1214 dehydrogenase 1199 Ribavirin 1022 recombined extension on truncated templates ribavirin, regioselective acylation of 310 (RETT) 137 riboflavin, enzymatic synthesis 1026 redox-active metal ions 92 ribonuclease A (RNase A) 710 redox racemization 50 ribonucleotide phosphohydrolases 1016, – dynamic kinetic resolution, principle 1017 of 1385 ribosomal peptidyltransferase 680 reduced putidaredoxin (PDx) ribosome-binding site (RBS) 583 – cathodic regeneration of 1294 ribulose 5-phosphate 938 reduction processes using isolated Rieske cis-diol dioxygenases (RDO) 1241 enzymes 1211 – catalyzed oxyfunctionalizations 1243 – enzyme-coupled cofactor Rieske dioxygenases 1273 regeneration 1214–1218 Rieske ferredoxins 1498 – in situ cofactor regeneration, approaches Rieske non-heme iron dioxygenase for 1211, 1212 systems 1492 – substrate-coupled cofactor Rieske oxygenases 1273 regeneration 1212, 1213 Rieske-type ferredoxin protein 1496 reduction processes using whole cells 1205, ring-cleavage dioxygenase-catalyzed 1209–1211 reactions 1490 reductive amination in industry 1218–1220 ortho/meta-ring-cleavage dioxygenases 1501 reductive amination of keto acids – enzymology of 1502 1165–1170 ring cleavage enzymes 1517 – a-amino acid dehydrogenases ring-opening polymerization (ROP) 1809, ––NAD(P)-dependent 1167, 1168 1841 ––reaction scheme of 1166 – enzyme-catalyzed 1811 – under in situ cofactor regeneration 1166 rivastigmine 316 reductive cofactor 12 RNA-abzymes 1748 para regioselectivity 1562 RNA-based ribozymes 908 regioselectivity/diastereoselectivity 14 RNA polymerase ribozyme, evolution of 119 regulatory process 594 Rnase activity 1767 renal dehydroxypeptidase inhibitor 569 RNase inhibitors 1753 repetitive batch processing (RBP) 226 rolling circle amplification (RCA) 124 (R)-ethyl 3-hydroxybutyrate 1213 RosettaMatch algorithm 1722 rhamnose inducible promoter 604 Rossmann fold 1409 rhamnulose-1-phosphate aldolase Ru-based racemization/epimerization (RhaD) 880, 881, 1369 catalyst 330 Rhizomucor pusillus 1897 ruthenium(II) tris(bipyridine) Rhizopus arrhizus 1256 complexes 1340 Rhizopus japonicus 1908 Rh-mediated FAD regeneration 1445 s rhodium 39 Saccharomyces cerevisiae 17, 19, 767, 991, 993, Rhodococcus corallinus B-276 1498 1093, 1190, 1837 Rhodococcus equi NCIMB 40213 cells 573 Salinispora tropica 1575 1980j Index

Salmonella enterica 1024 short-chain dehydrogenases/reductases sarcosine 1554 (SDRs) 1038, 1041, 1042, 1143 saxagliptin 1193 shuffling see DNA shuffling and gene shuffling SCHEMA/FamClash, hybrid of 149 sialic acid aldolase. See N-acetylneuraminic Schiff base 577, 770 acid aldolase (NeuA) Schiff’s reagent 402 sialic acids Schizophyllum commune 1819 – importance 868 Schizosaccharomyces pombe 17, 1256 – preparation 866 Scientific Protein Laboratories, enzyme sialic acid synthesis 871, 872 production 1904 Sialyl LewisX-related selectin inhibitor 884 – contact information 1904 simple alkyl galactosides 883 – hydrolases 1905 simvastatin, enzymatic synthesis 323 scleroderma 1748 single-crystal X-ray diffraction analysis 935 Screening Kits 1878 single-electron transfer (SET) reactions screening tissue extracts 1358, 1361 – traditional approach 951 single-molecule- PCR-linked in vitro scytalone dehydratase 484, 485 expression (SIMPLEX) 135 SDS-PAGE enzyme 586 sitagliptin 804 sec-alcohols/amines, deracemization 62, – metal-catalyzed, comparison of 36 1391 site-specific mRNA binding proteins 476 secologanin 770 SN2 inversion of alcohol 264 secondary cyclic meso-diols, desymmetrization sodium borohydride 12 of 348–350 sodium dioctyl sulfosuccinate (AOT) 1094 secretory proteins 689 Solanum tuberosum 405 (R)-selective amidase (RamA) 583 sol–gel matrix 952 D-selective amino acid amidase 604 solid/gas system 932 L-selective lactamase 570 – bioreactor system 929 selenosubtilisin 1720, 1721 solketal 305 semi-rational approach 970 soluble enzymes, alternative reactors – mutagenesis approach 537 for 225–227 sequence homology-based screening soluble methane monooxygenase techniques 75 (sMMO) 1270 sequence–structure–function – catalytic cycle of 1271 relationships 103 solvent-free esterification 511, 513 serine 1011 solvent resistant aminopeptidases 579 L-serine Sorangium cellulosum 1255 – PLP-dependent deamination SORONA polymer 473 mechanism 482 sortase-mediated ligation 697 serine dehydratases 482, 765 (S)-specific enoyl-CoA hydratase – proposed mechanism 767 – reaction mechanism 489 serine dehydrogenase 1177 (S)-specific 2-enoyl-CoA hydratase 1 serine hydratases 769 (ECH 1) 489 serine hydrolases 1696, 1703, 1704, 1745 (R)-specific enoyl-CoA hydratase reaction serine hydroxymethyltransferase mechanism 490 (SHMT) 901 (R)-specific hydroxynitrile lyase serine peptidases 680–682, 686, 690, 691 (HNL) 993 – subsite–substrate interactions 704 (S)-specific NADH-Dependent ADH from serine racemase 1611 horse liver 1042 Ser53Pro/Leu162Gly 146 (R)-Specific NADH-Dependent ADH from Servi’s rules, reduction in bakers’ yeast 1114 Nocardia globerula 1046, 1047 SeSaM methods 125 (S)-specific NADH-Dependent ADH from Shigella flexneri 1024 Rhodococcus erythropolis 1044, 1045 shikimate pathway 484 (S)-specific NADH-Dependent ADH from Shine–Dalgarno sequence (SD) 77 Rhodococcus ruber 1045, 1046 Index j1981

(S)-specific NADH-Dependent ADH from Streptomyces thioluteus 1561 Sporobolomyces salmonicolor 1047, 1048 strictosidine synthase 770 (R)-specific NADPH-Dependent ADH from structural classification of proteins (SCOP) 69 Candida magnolia 1047 structure-stabilizing effect 948 (R)-specific NADPH-Dependent ADH from StyA regeneration approaches Lactobacillus kefir and L. brevis 1043, 1044 – catalytic performance of 1293 (S)-specific NADPH-Dependent ADH from styrene monooxygenase (StyAB) Thermoanaerobacter sp. 1042, 1043 – substrate scope of 1291 (S)-specific NADPH-Dependent ADH Gre2p styrenes, epoxidation of 7 from Saccharomyces cerevisiae 1046 styrene to 5-exo-hydroxycamphor 1414 spectroscopic assay 971 styrene-type epoxides sphingosine mimetics – two-enzyme catalyzed hydrolysis of 54 – preparation, ThrA catalysis application 904 a-substituted amides Spiegelmann’s RNA molecules 119 – resolution 611 spiro-annulated sugars 883 p-substituted thioanisols 1558 S-pocket 924 substrate activation phenomenon 546 stability/solubility substrate-coupled cofactor- – prediction and engineering of 96 regeneration 1050 staggered extension process (StEP) 136 substrate-coupled regeneration approach 1336 standard free energies substrate–enzyme interactions 93 – of hydrolysis for common metabolites 1006 substrate feeding product removal (SFPR) standard synthetic tool 35 method 1447 Staphylococcus aureus 721 substrate–metal complex 536 Staphylococcus epidermidis 1214 substrate specificity, of amino group oxidizing Stenotrophomonas maltophilia 1815 enzymes 1562 Stenotrophomonas maltrophilia 769 subtiligases 710 stereochemistry 258–261 subtilisin 1701 stereo-complementary aldol additions 902 o-succinoyl benzoate synthase 1719 stereo-complementary enzymes 858 (1R,6R)-2-succinyl-5-enolpyruvyl-6-hydroxy-3- stereoinversions 1391, 1392 cyclohexadiene-1-carboxylate stereoselective N-carbamoyl-a-amino acid (SEPHCHC) 924 amidohydrolases 653 2-succinyl-5-enolpyruvyl-6-hydroxy-3- stereoselective dihydroxylation 1307 cyclohexene-1-carboxylate stereoselective enzymatic desymmetrizations (SEPHCHC) 934 (SEDs) 46, 50 sugar stereoselective processes. See hydrolase- – derivative catalyzed by enolase 481 catalyzed processes – derivative dihydroxy-acid moiety 481 stereoselectivity 45, 882–895 – metabolism 479, 480 D-stereospecific amino acid amidase sugar coupling 1713–1715 (DAA) 600 sugar dehydratases 478 – catalytic mechanism 601 sugar derivatives 930, 931 steric factors 363 sugar nucleoside phosphates, synthesis steroid transformations 1257 of 432, 436–438 Stetter reaction 930 sugar v-phosphates Stetter-type reactions 933–935 – analogs 887 storage of enzymes 213 – stereoselective synthesis, complementary – in liquids 213 routes for 887 – in solids 213, 214 (S)-sulcatol derivative Stratagene’s QuikChange Multi Site-Directed – epoxidation of 1287 Mutagenesis Kit 129 Sulfolobus solfataricus 31, 1100 Streptomyces globisporus 1669 sulfoxidation 1553, 1556 Streptomyces griseoviridus 1243 – of methyl thioether substrates 1556 Streptomyces hygroscopicus 769 – of thioanisole 1557 Streptomyces lividans 78 sulfur-containing cyclic imides 668 1982j Index

symmetric (R)-benzoins – enzymatic one-pot synthesis 880 – enzymatic synthesis 932 tailor-made biocatalysts 561 syn/anti addition and elimination tailor-made enzymes reaction 468 – catalysts 909 synaptic complex – enzyme discovery, tools for 26–28 – stoichiometry 594 – enzyme screening, principles in 26 Syncore carries 1913 – organic syntheses 3 Syncore hydroxynitrile lyase enzymes 1909 – protein engineering methodologies 26, Syncore Laboratories, enzyme 28–31 production 1906 Talampanel 1211 – amidases 1911 Tanabe Inc. 662 – contact information 1906 Taq-polymerase 138 – Ene reductases 1906, 1907 – DNA polymerase, concentrations of 123 – formate dehydrogenase (FDH) 1912 target proteins, binding affinity of 91 – glucose dehydrogenase (GDH) 1912 tautomerization 471, 483 – glycosidases 1913 template-based modeling 95 – hydrolases 1913, 1914 terephthalic acid (TA) 1813 – hydroxynitrile lyase 1909, 1910 N-terminal methionine residue 602 – immobilized enzymes 1916 terpene biosynthesis, non-mevalonate – immobilized lipases 1915 pathway 931 – immobilized proteases 1916 terpenes, oxyfunctionalization of 1295 – ketoreductases 1907 terpenoids, biocatalytic oxidation of 1301 – nitrilases 1908, 1909 tertiary amines, enantioselective – nitrile hydratases 1908 oxidation 1548 – nitro reductases 1911 tetrahedral transition state, stabilization – transaminases 1910 548 Syncore library of amidases (ES-AMD) 1911 tetrahydropyranyl diols 347 Syncore library of nitrilases (ES-NIT) 1908 tetrahydropyranyl diols desymmetrization, Syncore library of nitrile hydratases scope study for 347 (ES-NHT) 1908 3,4,5,6-tetrahydropyridine-2-carboxylic Syncore library of nitro reductases acid 1197 (ES-NTR) 1911 2,2,6,6-tetramethyl-1-piperidinyloxyl Syncore v-transaminases (ES-ATA) 1910 (TEMPO) 1361 synthesis of TrusoptTM 1209 tetrathiafulvalene/tetracyanoquinodimethane synthetic polymers, functionalization (TTF/TCNQ) 1346 – limited enzymatic surface hydrolysis 1811 textile processing, enzyme-based products –– enzymatic grafting 1818, 1819 used for 1844 –– oxidoreductases, surface Thamnostylum piriforme 1256 modification 1817, 1818 ThDP-dependent 1-deoxy-D-xylulose –– polyacrylonitriles, enzymatic hydrolysis 5-phosphate synthase (DXPS) 931 of 1816, 1817 ThDP-dependent enzymes 922, 933, 935 –– poly(alkylene terephthalates) 1811–1814 – chemoselectivity 923 –– polyamides, enzymatic hydrolysis – potential 920 of 1814–1816 ThDP-dependent glyoxylate carboligase – polyesters, enzymatic synthesis 1808–1811 (GCL) 938 syringomycins 768 ThDP-dependent intermolecular systemic lupus erythematosis (SLE) 1748 1,4-addition 933 – DNA-hydrolyzing antibodies 1751 Thermoactinomyces intermedius 1187, 1192, 1193 t Thermoanaerobacter brockii 1022 tagatose 1,6-bisphosphate aldolase Thermobifida fusca 1556 (TagA) 880, 881 thermophilic microorganisms 555 – cleavage 880 Thermoplasma acidophilum 1210 – diastereoselectivity of 173 thermostable (þ)c-lactamase 572 Index j1983 thiamine diphosphate (ThDP) transaminases (TAs) technology 219, 779, – discovery 919 781, 802, 804 – structure 920 – amine-TA in action, for industrial thiamine, evolutionary emergence 919 scale 802, 803 thiamine pyrophosphate (TPP) 1418 ––in situ product removal 802 thiamphenicol 906 – applications of 806–810 thiazolin-5-ones 302 – assay methods, determine activity 787, 788 thioglycoligase 1714, 1715 – asymmetric synthesis with amine-TA 798 thioglycosynthases 1714 ––shifting equilibrium by removal of thiol ester hydrolases 503 coproduct 799–801 thiol-modifying reagents 586 ––shifting equilibrium by cyclization 798 thiophene-2-carboxaldehyde 1421 – asymmetric synthesis with a-TA 792 thiosugars synthesis 889 ––coupling with v-amino acid TA 795 5-thio-D-xylopyranose 888 ––decomposition of keto acid 5-thio-D-xylulofuranose 888 by-product 793, 794 threo-3-hydroxy-L-aspartate ––equilibrium shift in action 796, 797 ammonia-lyase 768 ––product precipitation 793 L-threonine ––recycling of amino donor via reductive – PLP-dependent deamination amination 794, 795 mechanism 482 ––synthesis of D-amino acids 795, 796 threonine dehydratases 482, 765 – classification based – proposed mechanism 767 ––sequence similarities and three- threshold limit value (TLV) 980 dimensional structures 783 thymine hydroxylase 1314 ––on substrate specificity 782, 783 tobacco 5-epi-aristolochene synthase – CuSO4/MeOH assay 786 (TEAS) 1712 – enantioselectivity 811 a-tocotrienol 343 – kinetic resolution with amine-TA 790–792 toluene/biphenyl family includes – mechanism of transamination reaction enzymes 1493 784 toluene dioxygenase (TDO) 1241, 1303, 1304, – methods to assay activity and 1495, 1557 enantioselectivity 784–788 toluene monooxygenases 1286 – occurrence and properties of 781 – toluene 3-monooxygenase (Tbu) 1498 – principle of transamination catalyzed – toluene 4-monooxygenase 1556 by 781 total turnover numbers (TTNs) 1287, 1335, – processes using 848–850 1506 – protein engineering for decreasing substrate toxin-co-regulated pilus (TCP) 594 and product inhibition 804, 805 Toyobo enzymes, enzyme production – protein engineering for increasing activity 1917 and thermostability 803, 804 – contact information 1917 – reaction cycle of 785 – dehydrogenases, nicotinamide- – scope and limitations of amine-TA 805 requiring 1924–1926 ––enantioselectivity 811 – distributors 1917–1919 ––enzyme availability 813 – hydrolases 1920, 1921 ––substrate scope 811–813 – hydroxylases 1924 – strategies in biocatalysis 788–790 – miscellaneous enzymes 1926 transcription regulators 594 – oxidases 1921–1924 transesterification 327 Trametes rigida 1557 transesterification polycondensation 1809 Trametes versicolor 1557 transferases 7 Trametes villosa 1557 – enzyme catalysis reactions 8 transaldolase 898–901 transformation of keto-acid, by whole-cell – metabolic function 899 biocatalysts 1219 transaldolase B (TalB) 899 transglutaminases 1824, 1825 transaminase-catalyzed reactions 790 transhydrocyanation reaction 953, 964–967 1984j Index

transition state analogs (TSAs) – contact information 1927 – immunization 1756 – dehydrogenases, nicotinamide- – induced abzymes 1737 requiring 1928, 1929 transketolase (TK) 930 – hydrolases 1928 – catalyzed carboligation reactions 930 – miscellaneous enzymes 1930 – evolution 931 Universal Protein Resource Knowledgebase – substrate range 931 (UniProt) 69 tricarboxylic acid (TCA) cycle 666 University of Minnesota Biocatalysis/ Trichaptum byssogenum 1557 Biodegradation Database (UM-BBD) 1487 2,4,6-trichlorophenol 4- monooxygenase a,b-unsaturated aldehydes 901 (TcpA) 1499 unsaturated amino acids 588 Trichoderma viridae 1197 a,b-unsaturated aromatic and aliphatic tricyclic microbial elicitor (þ)-syringolide 893 aldehydes carboligation 939 (3R,5R)-2,4,6-trideoxyhexose 863 d,e-unsaturated cyanohydrins, asymmetric trienes 1305 synthesis 949 3,3,3-trifluoro-2-amino-2- a,b-unsaturated ketone 481, 934 methylpropanamide 619 – PigD-catalyzed 1,4-addition of active (R)/(S)-3,3,3- trifluoro-2-hydroxy-2- acetaldehyde 935 methylpropionic acid (E)-a,b-unsaturated nitriles 551 – Lonza process for production, kinetic – (E/Z)-selective synthesis 552 resolution step 619 uracil/thymine dehydrogenase 668 (S)-3,3,3-trifluoro-2-hydroxy-2- urea protecting groups, removal of 1549 methylpropionic acid 618 b-ureidopropionase 663 trimethylethoxysilane 1702 uridine diphosphate glucuronic acid (UDPGA) 2,4,6-trinitrotoluene (TNT) 1129 transferase 515 1,3,5-triol derivatives 344, 345, 346 uridine 30-(p-nitrophenyl phosphate) 1747, triose phosphate isomerase (TIM) 31, 1753 1647, 1648 urocanase 476, 477 tris(hydroxymethyl)aminomethane UV–vis spectroscopy 121, 153 (Tris) 1011 Triton X-100 520 v trypsin 1702 valine 768 tryptase 842 Valley enzymes, production L-tryptophan synthase, production 519 – contact information 1930, 1931 turnover frequency (TF) 1338 – hydrolases 1931, 1932 two-enzyme cofactor recycling system, concept vanadate complexes 1554 of 1444 vapor-detector tubes 980 two-liquid phase biocatalysis (TLPB) 235 Vibrio fluvialis 798, 800 two-phase semi-continuous reactor vinyl acetate 340 (TPSCR) 1447 vinylaromatic compounds, conversion 1290 two-phase system 521 (R)-5-vinylpyrrolidone 573 – principle 979 viral infections 1004 tyrosinases 1548, 1553, 1555, 1557, 1824 virulence factors 579 tyrosine 1238 – formation 594

tyrosine 2,3-aminomutase 1667, 1668 vitamin B12 472 tyrosine hydroxylase 1238 vitamin B2-complex 507 V8 protease 722, 723 u Vmax value 752, 1199, 1538, 1686 ubiquitin-conjugate degrading enzyme (UCDEN) 690 w ultra-competent cells 127 water contact angle (WCA) 1814 ultrafiltration 198, 1214 water-immiscible organic solvents 13 UniProt database 781 Werlen system 1493 Unitaka, Ltd., enzyme production 1927 – classification scheme of 1494 Index j1985

Wernicke–Korsakoff syndrome 920 D-xylulose 5-phosphate whole-cell application 1445 – transketolase-catalyzed synthesis 896 whole-cell biocatalysts 571, 664 X-Zyme GmbH, enzyme production – advantage 587 – alcohol dehydrogenases 1935, 1936 whole-cell biotransformation for – amino acid dehydrogenases 1936 enantioselective reduction 1209 – contact information 1932 whole cell catalyst 555 – decarboxylases 1937 whole cell oxygenase biocatalysts solves 1507 – glycosyl transferases 1938 whole-cell transformations 1369 – hydrolases 1933 – representative selection of 1370–1372 – ketoreductases 1933, 1934 wild-type (WT) – lyases 1938 – enzymes 120, 139, 167 – NAD(P)H regeneration enzymes 1935 – isozymes 926 – oxidases 1937 wool fibers, hydrolysis 1825 y x yeast alcohol dehydrogenase (YADH) 800, xanthine oxidase, kinetic constants 1417 1330 xanthin oxidase 1414 YrpC isozyme 1622 Xanthobacter species 1286, 1298 – limonene enantiomers, epoxidation z of 1299 zeaxanthin 1254 fi xemilo ban hydrochloride 838 Z-Gly-Tyr-NH2 Xer-mediated site-specific – PAF catalyzed C-terminal activation 625 recombination 593 Z-Gly-Tyr-OMe Xolvone (1,5-dimethyl-2-piperidone) – PAF catalyzed C-terminal activation 625 – chemoenzymatic synthesis of 1841 ZmPDC – synthesis of 1840 – carboligase activity 925 þ x-ray analysis 572 Zn2 dependent homotetramers 880 þ x-ray crystallography 691 Zn2 ions 1011 x-ray photoelectron spectroscopy (XPS) – interactions of phosphate group with 1012 data 1813 zofenopril 336 x-ray techniques 67 Zygosaccharomyces rouxii 1209, 1210 xylanase A from Bacillus subtilis (XylA) 158 zymogens 676, 689, 715, 716 xylene monooxygenase 1236 Zymomonas mobilis 17, 800, 1299 – from P. putida mt-2 1517 (Z,Z)-nona-2,4-dienal xylose 152 – enzymatic disproportionation 1410