487

Index

a affinity chromatography with protein AB 468 tags 20–22 absorbance 8, 13, 36 affinity immobilization 70 acetonitrile 129, 131, 174, 254, 383, 418 agarose 12–14, 18, 66, 73–75, 81 acetophenone 104, 159, 162, 173, agarose bead technologies (ABT) 68 257, 335–336 Agrobacterium radiobacter AD1 (HHDH) 367 derivatives 335 Ajellomyces dermatitidis (AdRedAm) 376 N‐acetyl amino acrylate 408 D‐ 152, 153, 155, 372 N‐acetylneuraminic acid 414 alanine dehydrogenase (AlaDH) 153, 363, Acidithiobacillus caldus sucrose 389, 472 synthase 229 alcohol dehydrogenases (ADHs) 45, 276, Acinetobacter calcoaceticus (AcCHMO) 48, 332, 468, 471 202, 203, 208, 322, 393 disproportionation of Acinetobacter calcoaceticus NCIMB rac‐2‐phenylpropanal 209 9871 322 stereoselective reduction reactions active pharmaceutical ingredients atorvastatin 189 (APIs) 118, 121, 143, 174, 299, bulky‐bulky substrates 186 305–306, 361, 429–431, 431, 443, bulky‐non bulky substrates 186 449, 452 dynamic kinetic resolution Adaptive Laboratory Evolution (ALE) (DKR) 189–190 experiments 50 montelukast 188 adenosine 5′‐diphosphate ‘Prelog’ and ‘anti‐Prelog’ selectivity 185 (ADP) 229–230, 275 (S)‐alcohols 188, 190, 369, 374, 382 adenosine 5′‐monophosphate (AMP) 275 aldehyde 70, 128, 131, 133, 144, 152, 157, adenosine 5′‐triphosphate (ATP) 275 160–161, 167, 172–173, 190, 364, adenosine triphosphate (ATP) 282 378–379, 393, 419 adenylate kinase (AK) 96 aldehyde dehydrogenase (Ald‐DH) 379, ADH from horse liver (HLADH) 190–191, 389, 394 209–210, 263, 383 aldo‐keto reductases (AKR) 184 Advanced Enzymes Technologies, Ltd. 480 aldol condensation reaction 117, 128, Aerococcus viridans (S)‐α‐HAO 367 129, 133

Biocatalysis for Practitioners: Techniques, Reactions and Applications, First Edition. Edited by Gonzalo de Gonzalo and Iván Lavandera. © 2021 WILEY-VCH GmbH. Published 2021 by WILEY-VCH GmbH.

deGonzalo_bindex.indd 487 17-03-2021 20:34:27 488 Index

aldol reaction ω‐transaminases 172 C‐C ligations 126 (AmDH) 144, 145, 130–134 155–162, 172–173, 368, 369, 371, PPL and RNL 135–136 390, 472 algal fatty acid photodecarboxylase 328 amine‐form pyridoxamine (PMP) 152, 415 alkane hydroxylation 322–326 amine oxidases alkane oxyfunctionalization 324 desymmetrisation of meso‐ alkane production 328–330 compounds 152, 440 1‐alkene:β‐hydroxy acid 328 flavin‐dependent 149–150 alkene production 327–328 kinetic resolution and alkenes monooxygenases 204, 206 deracemisation 150–151 alkyl cycloalkenecarboxylates 386 one‐pot one‐ oxidative Pictet– allosterically controlled Kemp eliminase Spengler approach, (AlleyCat) 43, 44 deracemisation 151–152 allylamine 364, 369 amine synthesis 143, 156, 162, 174, 175, N‐allylcyclohexylamine 369 343, 363–365, 368, 410 allylic alcohols 204, 205, 266, 310, 370, 381, amine transaminase/acyl 382, 412 cascade 366 allylic amines 369 amine transaminases (ATAs) 48, 89, 98, 349, allylic epoxy alcohols 381 363, 368, 369, 370, 371, 372, 373, 374, Almac 468 376, 383, 468 Amano Enzyme Co., Ltd 480 d‐amino acid aminotransferase 385 (R)‐amide 149, 306 l‐amino acid deaminase 385 amination of alcohols 368–371 (S)‐α‐amino acids 394 amine(s) l‐α‐amino acids 408 144, 162–167, 173 amino acid synthesis 383–386, 392, 393 α‐chiral amines 143–144 l‐amino acylase‐catalyzed hydrolytic cytochrome P450s 169–171, 174 resolution 408 dehydrogenases 155–162, 172–173 aminoacylases 117, 118, 470 hydrolases (2R,4R)‐amino alcohol 374 BASF industrial scale KR of (S)‐β‐amino alcohols 394 α‐methylbenzylamine 148–149 amino alcohol synthesis 372–374, 389 dynamic kinetic resolution 146–148 (R)‐2‐aminobutanoic acid 385 kinetic resolution 145–146 ω‐amino carboxylic acids 392 norsertraline 149 4‐aminocyclohexanol 364 norsertraline intermediate 171 (1S,2R)‐2‐amino‐1‐(2,5‐dimethoxyphenyl) rac‐methylbenzylamine, kinetic propan‐1‐ol 372 resolution 171 amino ether 433 serine protease family 145 (S)‐2‐amino‐3‐(3‐fluorophenyl)propanoic imine reductases 155, 172 acid 386 monoamine oxidases 172 (R)‐2‐aminohexanedioic acid 385 oxidases 149–152 6‐amino hexanoic acid 392–393 Pictet–Spenglerases 167–169, 173–174 rac‐1‐aminoindane 119 reductive aminases 155–162 (1S,3S)‐1‐amino‐3‐methylcyclohexane 374 transaminases 144, 152–155 (Z)‐12‐aminooctadec‐9‐enoic acid 364

deGonzalo_bindex.indd 488 17-03-2021 20:34:28 Index 489

2‐amino‐2‐phenylethan‐1‐ol 374 asparagine (Asn) 193, 194, 336, 448 4‐amino‐1‐phenylpentane‐1‐ol 373 aspartase 163–164, 166 1‐aminotetraline 307 l‐aspartate 122, 166 aminotransferases 144, 152–155 aspartate ammonia lyases 162–167 ammonia lyase (PAL) 144, 162–167, 173, Aspergillus fumigatus 410 386, 388, 389, 394, 474 Aspergillus fumigatus (AfLCAO) 363 ammonium fumarate 166 Aspergillus melleus 131, 408 ammonium sulfate fractionation 4, 6–7, 15 Aspergillus oryzae (AspRedAm) 157, 364, α‐monobenzoate glycerol (α‐MBG) 7 369, 370, 451 amorphous carbon nitride (ACN) 289, 290, Aspergillus terreus 348, 349 344, 345 Assembly of Designed Oligonucleotides amorphous organic monomer (ADO) 35 assembly 290 AstraZeneca 121, 435 amphiphilic molecules 96 asymmetric carbon‐carbon bond amylases 3, 474, 476, 480, 481 formation 413 α‐amylases 476 asymmetric organocatalysis 413, 414 Anabaena variabilis (AvPAL) 386 asymmetric organocatalytic Mannich‐type analytical gel filtration 5, 21 reaction 414 Ancestral Sequence Reconstruction asymmetric radical dehalogenation 345 (ASR) 38 atorvastatin 189 anion‐exchange chromatography 7, 235 Aumgene Biosciences 481 4‐anisaldehyde 383 2‐azaadamantane N‐oxyl (AZADO) 416

anodized TiO2 nanotube array 287 AZD6738 435 antenna protein 283 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐ antihypertensive Dilevalol 307 sulfonic acid) (ABTS) 278 anti‐Markovnikov alkene Azotobacter vinelandii 15, 20 hydroamination 388 antipode (S)‐1‐phenylethane‐1,2‐diol 394 b “anti‐Prelog” ADHs 182, 185 Bacillus licheniformis 131, 310 apparent kinetic parameters 76–77 Bacillus megaterium 47, 170, 253, 256, 324, aqueous superabsorber matrix 419 348, 373, 376 Arabidopsis thaliana 19, 367 Bacillus megaterium transaminase Archaea microorganisms 116 (BmTA) 373, 376 aromatic aldehyde 419 Bacillus sphaericus (D‐ATA) 385 aromatic amino acid ammonia lyases and Bacillus subtilis (BsPAD) 101, 106, 172, 254, mutases 164, 165 337, 380 Aromatoleum aromaticum alcohol Bacillus subtilis ERED 380 dehydrogenase (AaADH) 368–369 Baeyer–Villiger monooxygenase artificial recycling photosystem 326 (BVMO) 20, 21, 47, 198, 200, 201, artificial enzymes 115 204, 207, 208, 210–211, 379, 380, 387, artificial transfer hydrogenase 392, 435, 436, 468 (ATHase) 372 asymmetric sulfoxidation 211 (R)‐β‐arylalanines 386 biocatalytic applications and prototypical aryl alcohol oxidases (AAO) 20, 349 199–200 1‐arylprop‐2‐yn‐1‐ols 382 Criegee intermediate 199

deGonzalo_bindex.indd 489 17-03-2021 20:34:28 490 Index

Baeyer–Villiger monooxygenase transesterification 304–305 (BVMO) (Contd.) nonaqueous media 247–267 FMN‐dependent and specific for in pharmaceutical industry 430–442 NADH 199 biocatalysts 275, 469 kinetic resolution of a racemic heterogeneous 419–420 ketone 210–211 hydrolases 468 NADPH‐specific FAD‐dependent immobilization techniques 63–82 monooxygenases 199 industrial processes 429–460 practical approach 203–204 stability stereoselectivity 201–203 half‐life time of biocatalysts 78 Baeyer–Villiger (BV) oxidation 115, 126, residual activity 77 182, 198–200, 206, 321–322, 436 stabilization factor 79 benzaldehyde lyase (BAL) 349 TTN 77–78 catalysed carboligation 377 types of 450 benzoin derivatives 378 biocatalytically‐inactive NAD(P)H isomers benzoylformate decarboxylase variant and dimers 332 L461A 378 biodiesel 99, 100, 254, 388 (S)‐benzylamide 311 biotransformations 63, 209–211, 408–419 benzylamine 126, 158, 311, 364, 389 (R)‐biphenylalanine 442–445, 447, 1‐benzyl‐3‐carbamoylpyridinium bromide 452, 454–455 (mNAD+) 340 biphenylpyruvic acid 443, 444, 445, 455 N‐benzyl‐2‐methoxyacetamide 366 2,2′‐bipyridyl‐containing poly(arylene‐ berberine bridge enzyme (BBE)‐catalysed ethynylene)‐alt‐poly(arylene‐vinylene) aerobic C–H activation 371 polymer 284 BetaCavityWeb 49 bisulfite adduct 441 biaryl alcohol 409, 410 boceprevir 152, 439–442 biaryl and alkene compounds 409 N‐Boc‐piperidin‐4‐one 20 biaryl ketones 409 Bornscheuer′s group 48, 155, 306, 410, 419 biaryl‐substituted amines 410 bovine pancreatic lipase (BPL) 129 bicyclic lactone 48 branched‐chain alcohol dehydrogenase 12 bienzymatic linear cascades 365–366 2‐bromobenzaldehyde 390 bio‐affinity chromatography 11–14, 18 (S)‐2‐bromo‐2‐cyclohexen‐1‐ol 276 bio‐based liquids Burkholderia cepacia 254, 309

CO2‐expanded 264–265 Burkholderia (formerly Pseudomonas) cepacia CPME 261–262 lipase (BCL) 310 MeTHF 260–261 1,4‐butanediol (1,4‐BD) 258 potential application for 262 2,3‐butanediol dehydrogenase (BDHA) 389 biocatalysis (R)‐sec‐butylamine 11 advances of 275 butyl hexanoate 302 compartmentalization in 89–108 (R)‐2‐[(S)‐sec‐butyl]piperidine 375 under continuous‐flow conditions asymmetric synthesis 311–312 c dynamic kinetic resolutions 310–311 cadmium sulfide [CdS] 278, 285, 287 esterification 301–304 1‐caffeoylglycerol 9 kinetic resolutions 305–310 CAL‐B (CAL‐B@SNFs‐PE) 100

deGonzalo_bindex.indd 490 17-03-2021 20:34:28 Index 491

CAL‐B Ser105Ala mutant 128, 129, 265 centrifugal partition reactor (CPR) 302, 303, calcium carbonate microspheres 287 324, 326, 330 calmodulin 40, 43, 44 C‐glucosyltransferase reaction 229 Candida antarctica 122 C‐glycosylation of phloretin 229 Candida antarctica lipase A (CAL‐A) 15, charge transfer pathway 280 310, 383 chemically converted graphene Candida antarctica lipase B (CAL‐B) 76, (CCG) 284, 335 99–100, 117, 122, 124–126, 128–130, chemical mutagenesis 35 133–134, 149, 171, 251, 365, 469, 478 chemical regeneration method 276, 279 Candida freundii (CfTPL) 384, 392 chemoenzymatic cascade Candida parapsilosis carbonyl reductase reactions 92, 101 (CPCR) 257 chemoenzymatic cascades 90, 92, 93, 96, 97, Candida rugosa lipase (CRL) 119, 260, 100, 101, 105, 266, 405, 407 262, 310 Chemophor• 383 catalyzed hydrolysis 260 chimeric amine dehydrogenase ε‐caprolactam hydrolysis 392 (Chi1AmDH) 368, 369

carbon‐doped TiO2 279, 285 chiral alcohols 98, 106, 107, 212, 312, 332, carbon dots (CDs) 285, 286, 340, 341, 342 335, 349, 377, 411, 436, 437 carbon nanodot (CND) 285, 290, 340, 342 chiral amines 143, 144, 145, 149, 150, 153, catalyst 325 155, 158, 160, 162, 174, 175, 306, 307, carbon nanodots‐silica hybrid 348, 349, 363, 368, 369, 371, 374, 391, semiconductors (CNDSH) 285 416, 417, 420, 458, 472 carbon nitrides 288, 289, 319, 345 synthesis 306 carbonyl reductase (CR) 184, 253, 257, 364, α‐chiral amines 143–145, 149–150, 153, 155, 374, 389 158, 160, 174–175, 307 carbonyl reduction 182, 332–336, 349, 377, chiral biaryl alcohols 409 379, 380, 387, 392 chiral diamine 414 carvolactones 380 chiral 3‐oxoesters 386 cascade chemo‐enzymatic/multi‐enzymatic chiral Zn(II) catalyst 413 reactions 313, 314 Chlamydomonas reinhardtii 332 cascade triacylglycerol 304 4‐chlorobenzylamine 389 catalytically active enzyme‐bound flavin (–)‐chlorodiisopinocampheylborane

(FMNH2) 336, 337, 379 437, 439 catalytically active flavin 341 chlorophyll 283, 319 catalytic promiscuity 116–117, 122–130, chloroplast matrix 282 133, 134, 137, 166 chloroplast membranes 282 catalytic worlds 90 chromatography media 22, 24 CAVER 49 Chromobacterium violaceum (CvTA) 98, C2‐centered α‐amino alkyl radical 342 172, 363, 374, 389 CCGCMAQSP 283, 284, 333, 335 Chromobacterium violaceum TA variant Celite• 365 (Cv2025 TA) 376 cell‐free cytochrome P450 solution 326 α‐chymotrypsin 126, 128, 254 cell‐free extracts (CFE) 5, 7, 81, 98, 168, 184, Cibacron Blue dye affinity matrix 12 187, 211, 259, 329, 468 cinnamic acid derivative 100, 166 cell lysates 448, 450, 455 cinnamic acids 97, 98, 100, 165, 166, 173

deGonzalo_bindex.indd 491 17-03-2021 20:34:28 492 Index

Citrobacter freundii (CfTPL) 384, 392 continuous‐flow protocols 299 classical enzymatic kinetic resolution 310 continuous flow synthesis 105, 302 c‐Lecta 469 copper‐dependent amine oxidases 149 Clostridium acetobutylicum corticotrophin‐releasing factor (CRF‐1) (CLAP450) 366 antagonist 307 Clustered Regularly Interspaced Short covalent binding 70, 253 Palindromic Repeats (CRISPR) covalent‐organic frameworks system 50 (COFs) 288, 290 Codexis, Inc. 90, 152, 155, 172, 188, 189, covalent triazine frameworks (CTFs) 290 2+ 207, 260, 364, 375, 381, 433, [Cp*Rh(bpy)(H2O)] 279, 326 460, 475–476 Cremophor EL• 98

CO2‐expanded bio‐based Criegee intermediate 199, 200 liquids 264–265, 267 cross‐linked enzyme aggregates cofactor 275 (CLEAs) 70 recycling 104, 187, 211, 326, 327, 331, C1‐shortened alkanes 328 334, 335, 336, 344, 375, 378, 382, 387, cyanide dihydratases 468 393, 413, 415 4‐cyanobenzaldehyde (4‐CNB) 135–136 regeneration efficiency 284 cyanuric acid‐melamine (CM) co‐immobilization 81, 92, 304, 362, 369, complex 289 374, 419 cyanuric chloride 290 column materials 14, 22–24 cyclic deracemization 143, 342, 343, 344 combination of photooxidation and cyclic ketones 130, 131, 201, 202, 203, 259, enzymatic transformation 348–351 321, 322 Combinatorial Saturation Test cycloalkenecarboxylates 386 (CASTing) 37, 38 cyclohexane‐1,4‐dione 364, 365 Combinatorial Saturation Mutagenesis cyclohexanone (CHX) 20, 48, 98, 131–132, (CSM) 37, 187 134, 135–136, 159, 160, 167, 199, 201, commercial carriers 68 202, 203, 208, 322, 338, 393 compartmentalization cyclohexanone monooxygenase (CHMO) 20, cell 93–94 48, 199, 202, 203, 208, 322, 393 classical enzyme immobilization 92 N‐cyclohexyl‐2‐aminoethanesulfonic acid concept of 89 (CHES) 366 continuous flow synthesis 105 2‐cyclohexyl‐1‐methyl‐1‐pyrrolinium micellar systems 96–100 iodide 344 molecular encapsulation 100 cyclopentyl methyl ether (CPME) 259, one pot reactions 92 261–262, 441 PDMS thimbles 104–105 cyclopropylamine 158, 364 pickering emulsions 98 cyclopropylethylamine 307 protein assemblies 95–96 cysteine (Cys) 17, 40, 42, 70, 81, 131, 170, tea‐bag synthetic technology 103–105 193, 384, 448

concurrent cascade 89, 90, 91, 105 cytochrome b6f complex 282 metal‐biocatalytic processes 90–91 cytochrome P450 20, 47, 49, 144, 169–171, conduction band (CB) 210, 280, 287, 338, 174, 204, 206, 207, 326, 384, 468, 469, 339, 341, 344 474, 481

deGonzalo_bindex.indd 492 17-03-2021 20:34:28 Index 493

catalysed hydroxylation 384 diastereomerically enriched monooxygenase 20, 47, 204, 206–207, N‐heterocycles 375 207, 323–324, 326, 366–367 diastereomeric anti‐ and syn‐aldols 135

cytochrome P411CHA 170–171, 174 diastereoselectivity, aldol reaction 131, 134, 135, 136, 194, 377, 419, 430, 431, 432, d 433, 459 Danisco• food enzymes 476 diatomite 288 D‐anti‐4,5‐dihydroxynorvaline 1,8‐diazabicycloundec‐7‐ene 311 (DHNV) 372, 373 diazotization–iodization processes 100 deacetalization–Henry process 100 1,4‐dicarbonyl alkene 412 deacetalization–Knoevenagel process 100 α,ω‐dicarboxylic acids 392 deacetoxylation 347–348 2,3‐dihydrofuran 415 DEAE‐Sepharose 8, 10, 17 dihydroxyacetone (DHA)‐dependent aldolase column 8 mutant Fsa1‐A129S 378 O‐dealkylation 326–327 (S)‐1‐(3,4‐dihydroxybenzyl)‐1,2,3,4‐ deazariboflavin (dRf) 334 tetrahydroisoquinoline‐6,7‐diol 376 decarboxylation 4,4′‐dihydroxystilbenes 100–101 alkane production 328–330 1,5‐dihydroxy‐1,2,3,4‐ alkene production 327–330 tetrahydronaphthalene 309 deep eutectic solvents (DES) 101, 106, 107, 2,6‐dimethoxy‐4‐allylphenol 367 248, 250, 251, 265–266, 303, 305, 320, 2,5‐dimethoxybenzaldehyde 373 352, 410 dimethyl carbonate 304 dehalogenation 189, 345–347 dimethylsulfoxide (DMSO) 129, 153, 172, dehydrogenases 174, 210, 211, 232, 233, 253, 256, 329, alcohol 185–187, 209–210 330, 331, 336, 346, 351, 365, 367, 370, amine 155–162, 172–173 371, 387, 413, 433, 434, 435, 453 de novo design 40, 50 1,3‐diols 413, 419 de novo enzyme design 34, 39–40, 50 dioxygenases 8–9, 482 fragment‐based computational directed enzyme evolution 95, 275, 459 design 39–40 directed evolution (DE) 33 minimalist approach 39 advantage of 34 minimalistic approaches 40 definition 34–35 rational parametric design 40 de novo enzyme design 34 rational parametric design of functional genetic recombination 35 assemblies 39 (ultra)high‐throughput screening and Rosetta model 40 selection 35–36 2‐deoxyribose 5‐phosphate aldolase non‐homologous recombination 35 (DERA) 130 non‐recombining 34 deracemisation of amines 371–372 pH‐dependent inactivation 36–37 deracemisation of alcohols 106 random approach 33–34 dialkyl glyoxylamide 414 random mutagenesis approaches 34–35 2,2‐diallylmalonate 411 recombining methods 34 α,ω‐diamine transaminase (YgjG) 365 solvent tolerance 36 diaphorase 80 thermostability 36–37

deGonzalo_bindex.indd 493 17-03-2021 20:34:28 494 Index

direct regeneration method 276 enantiopure l‐phenylglycine 393 2,5‐disubstituted pyrrolidines 375 enantiopure D‐mandelate dehydrogenase (DMDH) 393 (2R,5S)‐2‐methyl‐5‐ DNA (or gene) shuffling 35 phenylpyrrolidine 376 donor‐acceptor electron transfer enantiopure (R)‐2‐pentanamine 369 mechanism 288, 290 enantiopure (R)‐phenylglycidol 389 1 doped TiO2 279, 285, 286, 319, 339 enantioselectively provide Δ ‐pyrroline 439 double‐stranded DNA (dsDNA) 35 enantioselectivity d‐phenylglycine aminotransferase of biocatalysts 37–39 (DpgAT) 393, 394 of bulky–bulky ketones 266 DSM 166, 186, 253, 258, 381, 392, 475 of enzyme 151 DuPont 476 value 262 Dupont Nutrition & Biosciences 476 ENARASE• 469 dynamic kinetic resolutions (DKRs) 14, 89, endocyclic tertiary alcohol 387 118, 119, 143, 146, 189–190, 310–311 endotoxins 449, 451 dynamic membraneless compartments 96 ene‐reductases (ERs or EREDs) 183, 191, 198, 335, 336, 349, 355, 374, 379, 380, e 472, 481 electrochemical regeneration energy currency 292 method 276, 279 Enginzyme AB 68, 307 electron mediator 278, 279, 283, 292, ensemble docking 41 327, 334 Enterobacter cloacae 339 electron‐withdrawing group (EWG) 192, environmental aspects 442, 453–454 193, 195, 196 enzymatic commercial sources enantio‐ and diastereomerically pure AB Enzymes 468 (2R,5S)‐2‐methyl‐5‐ Advanced Enzymes Technologies, alkylpyrrolidines 376 Ltd. 480 enantio‐ and diastereopure Almac 468 (1R,2R)‐1‐phenylpropane‐1,2‐ Amano Enzyme Co., Ltd. 480 diol 378 Aumgene Biosciences 481 enantioenriched Biocatalysts 469 2‐methyl‐1‐phenylpropan‐1‐ol 336 c‐Lecta 469 enantiomerically enriched diester 431 Codexis, Inc. 475–476 enantiomerically pure (–)‐ DSM 475 chlorodiisopinocampheylborane 437 Dupont Nutrition & Biosciences 476 enantiomerically pure ester acid 431, 439 EnzymeWorks 481 enantio‐ or diastereoselectivity 430 Enzymicals 470 enantiopure amines 119, 143, 146, Evoxx Technologies GmBH 470–471 306, 372 Groningen Enzyme and Coenzymes enantiopure (S)‐berbines 371 Company 471–472 enantiopure (R)‐1‐(3‐bromophenyl) IBEX Pharmaceuticals Inc. 476–477 ethylamine 370 Inofea AG 472 enantiopure (S)‐1‐(4‐bromophenyl) Johnson‐Matthey 472–473 propan‐1‐ol 383 Meito Sangyo Co., Ltd. 481 enantiopure (R)‐2‐heptanamine 369 Metgen Oy 473

deGonzalo_bindex.indd 494 17-03-2021 20:34:28 Index 495

MP Biomedicals 477 epoxidations 91, 115, 116, 126, 128, 129, Novozymes 474 169, 182, 189, 204–206, 207, 208, 265, Oriental Yeast 482 330–331, 381, 389, 390, 418 Prozomix 474–475 equipment cleaning 443, 455–456 Sigma‐Aldrich 477–478 equipment utilization and throughput Strem Chemicals, Inc. 478 time 442, 455 Takabio 482 error‐prone PCR (epPCR) 35 Toyobo Co., Ltd. 482–483 esomeprazole 207, 208, 435–436 Worthington Biochemical Corp. 479 esterification 46, 116, 124, 125, 126, 128, enzymatic ketone reduction 409, 410, 247, 248, 257, 261, 262, 263, 264, 411, 413 301–303, 304–305, 330, 415 enzymatic promiscuity 116, 134 7‐ethoxycoumarin 324, 326–327 enzymatic regeneration method 276 ethyl acetate 146, 210, 262, 305, 306, 311, enzyme‐bound flavin 336, 337, 338, 365, 439 339, 341 ethyl (S)‐3,4‐chloro‐3‐hydroxybutyrate 367 enzyme engineering 3, 33, 34, 35, 36, 37, 38, ethylenediamine‐N,N′‐disuccinic acid lyase 41, 42, 49, 51, 90, 165, 423 (EDDS lyase) 164, 166 enzyme engineering strategies ethyl 4‐oxo‐pent‐2‐enoates 380 de novo enzyme design 34 ethyl 4,4,4‐trifluoroacetoacetate 258 fragment‐based computational eugenol oxidase 19, 367 design 39–40 Eupergit• C 65 minimalistic approaches 39, 40 Evoxx Technologies GmBH 470–471 rational parametric design 39–40 expression system 253, 446, 451 Rosetta model 40 Eyring equation 300 powerful computational algorithms 37 EziG‐immobilized random approach 33 ω‐transaminases 308–309 rational enzyme design 34 calmodulin 43 f

enantiomerically pure fac‐Ir(ppy)3 319 synthesis 45–47 Fe3+/polyphenol‐coated melamine experimental assays for 41 precursor 289 identification of tunnels 48–49 ferredoxin (Fd) 282, 327, 332, 333 Kemp elimination 43 ferryl hydroxyl moiety 323–324 MD simulations 40–41 flavin 319 metalloproteins 45 dependent amine oxidases 149 molecular docking methods 40–41 dependent monooxygenase 199, 204, protein stability 42–43 206, 321 QM/MM techniques 40–41 flavin adenine dinucleotide (FAD) 10, 15, substrate scope 47–48 16, 17, 20, 21, 149, 150, 199, 207, 322, semi‐rational design 34, 37–38 324, 329, 330, 331, 337, 341, 435, enzyme release testing 456–457 436, 439 EnzymeWorks 481 flavin‐dependent ene‐reductases Enzymicals 470 (EREDs) 335, 336, 374, 375, 379, 380 • Enzzen Technology 472 flavin hydroquinone (FMNhq) Eosin Y 319, 324, 326 cofactor 335

deGonzalo_bindex.indd 495 17-03-2021 20:34:28 496 Index

flavin mononucleotide (FMN) 14, 21, 149, (GlDH/ 191, 192, 193, 199, 275, 324, 325, 328, GluDH) 344, 345, 393, 394 337, 338, 339 glutamine (Gln) 448 dependent proteins 191 glutathione transferase (GST) 20 flavin‐semiquinone intermediate 338 glycerin carbonate 304 Flavobacterium JS‐7 cells 17 glycerol dehydrogenase (GlyDH) 73, flavocytochrome c3 (fcc3) 341, 342 74, 75, 77 flavocytochromes 341 glycoaldehyde 372 flavoenzyme CvFAP 329 glycosylated natural products 225–227 flavoenzyme 4‐hydroxybenzoate glycosyltransferase cascades 3‐hydroxylase 8 enzyme expression 230–232 flavonoids 225, 227–228, 235, 237 flavonoids 227–228 flavoprotein (Fp) 15–16, 16, 20, 21, 282, 336 Leloir 227 flavoprotein alditol oxidase (AldO) 21 natural products 225–227 flow systems 106, 107, 302, 305, 306, 308, nothofagin production at 100 g 309, 313 scale 233–237 fluorescein 319 nothofagin synthesis 229–230 fluorescence 36, 459 solvent engineering, substrate fluorescence‐activated cell sorting (FACS) 36 solubilization 232–233 fluorescence‐activated droplets sorting glycosyltransferases 225–227, 228, 229, 230, (FADS) 36 231, 237, 481 fluorinated NADH (FNADH) 263 GmSuSy 229–233, 235 d‐4‐fluoroalanine 385 Golden Gate gene 50

4‐fluorobenzaldehyde 131 gold‐loaded TiO2 (Au‐TiO2) 324, 325, 337, 4‐fluorobenzylamine 389 339, 349, 351 d‐4‐fluorophenylglycine 394 graphene derivatized with focused random mutagenesis 34 multianthraquinone‐substituted formate dehydrogenase (FDH) 162, 172, porphyrin (CCGCMAQSP) 283, 173, 183, 276, 285, 325, 334, 387, 392 284, 335

fragment‐based computational design 39–40 graphitic carbon nitride (g‐C3N4) 288, fumarate 163, 164, 166, 196, 341, 342 289, 290 fused‐monooxygenase 390 COFs 290

fusion‐tags 20 g‐C3N4@ α‐Fe2O3/C core@shell photocatalyst 289 g nanorod 289 D‐galactoside derivative 420 green carriers 66

g‐C3N4 mesoporous spheres (CNMS) 288 green chemistry 50, 275, 302 gel‐filtration 4, 5, 6, 9–11, 15, 17, 21 Groningen Enzyme and Coenzymes genetic recombination 34, 35 Company (GECCO) 471–472 β‐glucanases 476 Gluconobacter oxydans (GoSCR) 389–390 h glucose dehydrogenase (GDH) 172, 189, haloalkane dehalogenases (DhaA) 49, 256 276, 336, 339, 345, 346, 347, 363, 372, halogenated aromatic aldehydes 131 381, 382, 384, 413, 437, 474 α‐halolactones 345 glucosidase 254 health 227, 445, 453, 456, 458, 459, 476

deGonzalo_bindex.indd 496 17-03-2021 20:34:28 Index 497

Heck reaction 106, 409, 410, 411, 424 catalytic promiscuity 116–117, 122–130 (Z)‐heptadec‐8‐ene 329 catalyze C–C bond formation heptan‐2‐amine racemates 374 reactions 125 heteroatom oxidation esterases 117–118 Baeyer–Villiger oxidation lipases 122 reactions 206–207 organic synthesis 118 heterogeneous biocatalysts 64, 65, 66, 67, proteases 118 68, 69, 72, 73, 74, 75, 76, 77, 79, 80, 82, hydrolytic enzymes 3, 122, 474, 481 312, 313, 419–420 hydrolytic KR 143 heterogeneous hydrophobic β central leaf rhodium‐diphosphane‐complex 408 composition 122 heterogeneous, titanium‐grafted silica hydrophobic interaction chromatography

catalyst Ti/SiO2 418 (HIC) 6, 14–15, 17, 18 heterogenized alcohol dehydrogenase 419 hydroquinone dioxygenase 7, 10 heterogenized chemocatalysts 418 γ‐hydroxy‐α‐amino acids 372 heterojunction 280, 285, 287, 289, 290 (S)‐α‐hydroxy acids 394 heterostructured photocatalysts 287 hydroxyapatite (HAP) high chemoselectivity 429, 430 chromatography 15–17 (–)‐himbacine 310 3‐hydroxybenzoate 6‐hydroxylase 11, 19

His6‐SUMO‐HMFO fusion 20 2‐hydroxycycloalkanone His‐tagged proteins 19–20 intermediates 379 histidine (His) 19, 44, 45, 70, 118, 122, 145, 7‐hydroxyheptanitrile 364 165, 312, 448 β‐hydroxy ketone 419 histidine‐tagged benzaldehyde lyase 312 (R)‐2‐hydroxy‐l‐phenyl‐propanone 312 homologous recombination methods 35 5‐hydroxymethylfurfural (5‐HMF) 261 horse liver alcohol dehydrogenase 5‐(hydroxymethyl)furfural oxidase (HLADH) 186, 191, 209, 210, 263, 276 (HFMO) 19–20 horseradish peroxidase (HRP) 96, 254, 367 hydroxynitrile lyases (HNL) 349, 383 HotSpot Wizard server 38 3‐hydroxyphenylacetate 6‐hydroxylase from Hydroclassified CSM (HCSM) 37 Flavobacterium JS‐7 17–18 hydrogen bond acceptor (HBA) 250 p‐hydroxyphenyl lactic acid hydrogen bond donor (HBD) 250, 251, 262 enantiomers 391–392 α/β‐ folding 122 4‐hydroxy‐5‐phenylpentan‐2‐one 373–374 hydrolases 467 (R)‐4‐hydroxy‐5‐phenylpentan‐2‐ aldol reaction 130–134 one 373–374 amines 2‐hydroxypropyl‐β‐ BASF industrial scale KR of cyclodextrin 233, 235–237 α‐methylbenzylamine 148 para‐hydroxystyrenes 100–101 dynamic kinetic resolution 146–148 hygrine 365 kinetic resolution 145–146 hyperthermostable laminarinase 19 norsertraline 149 norsertraline intermediate 171 i rac‐methylbenzylamine, kinetic IBEX Pharmaceuticals Inc 476 resolution 171 Ideonella sakaiensis 47 serine protease family 145 imine intermediate 143, 167

deGonzalo_bindex.indd 497 17-03-2021 20:34:28 498 Index

imine reductases (IREDs) 144, 145, k 155–162, 172–173, 363, 374, 375, 470, Kazlauskas model 121 474, 476, 481 Keep It Simple and Smart (KISS) 35 imine reduction 342–344, 372 Kemp elimination reaction 40, 43, 44 immobilization yield (IY) 72, 73, 82, 308 keto acid 333, 374, 391, 393, 443, 457 immobilized enzyme 64, 65, 66, 67, 68, 71, keto acid decarboxylase (KDC) 333 72, 73, 74, 75, 76–77, 79, 80, 81, 104, keto acid intermediate 374, 393 160, 305, 307, 309, 310, 420, 450 2‐keto‐3‐deoxy sugar acids 105–106 immobilized glucose 67 γ‐keto ester 380 immobilized metal affinity chromatography α‐ketoglutarate 344–345 (IMAC) 18–20 ketoisophorone 338, 339, 366, 367 impurities 6, 24, 445, 446–450, 451, 452 2‐ketoisovalerate 333 Incremental Truncation of the Creation of ketoreductases (KREDs) 16, 98, 184, 312, Hybrid enzYmes (ITCHY) 35 332, 345, 346, 349, 364, 373, 481 indirect regeneration method 276 “keyhole‐lock‐key” model 48–49 (S)‐2‐indolinecarboxylic acid 165, 166 kinetic resolutions (KRs) 9, 89, 118, 119, industrial applications 3, 33, 46, 63, 65, 107, 142, 189–190, 305–311, 371 115, 116, 136, 198, 225, 275, 276, 285, Kluyveromyces polysporus 186 405, 442, 443, 468, 469, 474, 482 Knoevenagel condensation 125, 128 Inofea AG 472 Knoevenagel reaction 125, 126 , 128 inorganic semiconductors 285–287, Kosmotropic salts 10, 14, 15 288, 290 in situ‐formed aldol adduct 413 l internally modified CdS‐QDs microcapsules laccase‐mediated oxidation 386 (CdS/PTi) 286, 287 laccase mediator systems 369, 370, 381, in vitro compartmentalization (IVC) 382, 387 methods 36 laccases 98, 369, 374, 471, 481 ion‐exchange chromatography (IEC) 4, 7, 8, laccase/TEMPO‐catalytic system 416 10, 15, 17, 18 β‐lactam antibiotics 65 ionic liquid 107, 247, 310, 320, 352, 410 Lactobacillus brevis alcohol dehydrogenase irreversible immobilization 64, 69 (LbADH) 184, 368 isobutanol 253, 333 Lactobacillus kefir alcohol dehydrogenase isolated enzyme 3, 63, 307, 448, 450, 451, (LkADH) 104, 184, 364 455, 468 Lactococcus lactis, 333 isolated salt 433 l‐amino acid dehydrogenase (L‐AADH)‐ 361, 467 catalysed reductive amination 393 isopropylamine (IPA) 312, 313, 348, 349, L. confuses DSM 20196 392 370, 390, 416, 433, 434, 435, 444, 454 Leloir glycosyltransferases 225–228, 230, (S)‐2‐isopropylpiperidine 375 231, 237 Iterative Saturation Mutagenesis (R)‐levodione 339–340 (ISM) 37, 38 361, 467 light‐driven cofactor recycling j approach 326, 344 Jeotgalicoccus sp. ATCC 8456 327 light‐driven thio‐Michael addition 351 Johnson‐Matthey 472–473 (–)‐limonene 418

deGonzalo_bindex.indd 498 17-03-2021 20:34:28 Index 499

limonene epoxide hydrolase 418 Merck KGaA 68, 477 Lineweaver–Burk plot 76 metal‐ and biocatalysis 320 lipase from pig pancreas (PPL) 119, 125, 130 metal‐ and photocatalysis 320 lipases 116, 122 metal‐catalyzed alkene mediated promiscuous reactions 126, 128 hydroformylation 421 solvent‐free system 257 metalloproteins 45 lipidic plastoquinone molecules 282 metal organic frameworks (MOFs) 79 lipoamide dehydrogenase 10, 15 Metgen Oy 473 lipoglycans 449 methionine (Met) 448 lipophilic organisms 253 (S)‐4‐methoxymandelonitrile benzoate 383 lipopolysaccharides 449 1‐(4‐methoxyphenyl)butan‐2‐ol 368

liquid CO2 248, 250, 262–263, 267 ortho‐methylacetophenone 336 l‐lactate dehydrogenase (L‐LDH) 80 3‐methylaspartate ammonia l‐lysine AADH (LysEDH) 159, 162 lyases 163–164 Lobucavir 125, 126 (1S,3S)‐ and long‐chain dehydrogenase/reductases (1R,3S)‐3‐methylcyclohexanol 387 (LDR) 184 (R)‐2‐methylcyclohexanone 338 low complexity domains (LCDs) 96 (S)‐3‐methylcyclohexan‐1‐one 382 lowest unoccupied molecular orbital 1‐methylcyclohex‐2‐en‐1‐ol 387 (LUMO) 280 2‐methylcyclohex‐2‐enone 338, 340, 374 L. paracasei (L‐Hic) 392 3‐methylcyclohex‐2‐enone 374 lyases 144, 162–167, 173, 349, 361, 372, 377, methyl 378, 467, 474 4‐deoxy‐6‐aldehydo‐β‐D‐xylo‐ lyophilization 96, 98, 251, 252, 254, 450, 477 hexapyranoside 420 lyophilized enzymes 71, 457 1‐methyl‐3,4‐dihydroisoquinoline 344, 372 lyophilized (isolated) enzymes 448 1‐methyl‐3,4‐dihydroisoquinoline (MDQ) 344, 372 m methylene blue 319, 325 Machine Learning techniques 37, 38 5‐methylene‐3,5‐dihydro‐4H‐imidazol‐4‐one maltose‐binding protein (MBP) 20–21 (MIO) 163 mandelate racemase (MR) 393, 394 methyl ester 167, 260, 330, 387, 432, (S)‐mandelic acid 395 441, 442 Manihot esculenta hydroxyl nitrile lyase Methylovorus sp. strain MP688 19, 20 (MeHNL) 383 (E)‐2‐methyl‐3‐phenylacrylaldehyde 379 Mannich reaction 115, 117, 126, 127, 365, (S)‐3‐methyl‐4‐phenylbutan‐2‐one 382 366, 414, 415 (E)‐3‐methyl‐4‐phenylbut‐3‐en‐2‐ol 382 mass spectrometry 5, 21 (S)‐2‐methyl‐3‐phenylpropanoic acid 379 MBP‐TtProDH 21 2‐methyl‐1‐phenylprop‐2‐en‐1‐one 336

mediator Ru(trpy)Cl3 283 β‐methylstyrene 390 medium‐chain dehydrogenase/reductases 2‐methyltetrahydrofuran (MeTHF) 250, (MDR) 184, 192 260–261, 264 Meito Sangyo Co., Ltd 481 (R)‐1‐methyl‐1,2,3,4‐tetrahydroisoquinoline membrane‐associated proline (MTQ) 372 dehydrogenase 21 α‐methyltryptamine intermediates 377 1,3‐mercaptoalkanols 351 methyl viologen 278, 334, 338

deGonzalo_bindex.indd 499 17-03-2021 20:34:28 500 Index

micellar 96 2‐(N‐morpholino)ethanesulfonic acid Michael addition reaction 129 (MES) 342 Michael additions 115, 117, 126, 128, 129, 351 3‐(N‐morpholino)propanesulfonic acid Michaelis–Menten complex 45 (MOPS) 12 micro‐aqueous system 258–259 (3‐(N‐morpholino)propanesulfonic acid)‐ microbial cells 4, 452 based buffer 322 microbial enzymes 467, 480 MP Biomedicals 477 microcapillary single‐cell analysis and laser Mucor miehei lipase (MML) 126, 133 extraction (μSCALE) 36 multianthraquinone substituted porphyrins Micrococcus luteus alcohol dehydrogenase (MAQSP) 284 (MlADH) 364 multi‐catalytic reactions 93 microsomal epoxide hydrolase (mEH) 46 multienzymatic transformations 361–395 mild reaction conditions 361, 377, 395, 429, multi‐enzyme cascade reactions 90, 103 430, 446, 459 Multiple Sequence Alignment (MSA) 38, 39 “minimal DES” system 266 Mycobacterium smegmatis acyltransferase minimalist approach 39 (MsAcT) 125, 366 mixed cultures 93, 94 MOLE 49 n

molecular biology techniques 90, 115 (Na3[Ir(sppy)3]3) 342 molecular docking methods 41 NADP+ 104, 161, 172, 187, 191, 282, 327, molecular encapsulation 100 332, 335, 346, 347, 436, 437 molecular memory 252 NAD(P)H dependent enzymes 276 (MAO‐N‐9) 119, 143, NAD(P)H regeneration 183, 276, 283, 287 145, 149, 150, 172, 343, 371, 372, 376, NAD(P)H regeneration efficiency 287 439, 441, 474, 476, 481 1,4‐NAD(P)H regioisomer 276 monoamine oxidase N from Aspergillus niger NADPH‐specific ferredoxin‐NADP+ (MAO‐N) 150, 151, 160, 169, 172, reductase (FNR) 332, 333, 334 343, 371, 376 nanoparticles immobilization 254 monoamine oxidases (MAO) 172, 371, 384 natural deep eutectic solvents monoaminoethyl‐N‐aminoethyl (MANAE)‐ (NADES) 248, 251, 262, 265–266, 267 agarose carrier 73 natural nicotinamide cofactors 183, 340 mono‐ and disubstituted chiral natural polymers 66 piperidines 391 natural products, glycosylated 225–227 monoliths 67 nature photosensitizers 282, 283 monooxygenase N‐doped carbon nanodots (N‐CDs) 285, cyclohexanone 20, 48, 199, 202, 203, 208, 286, 340 322, 393 2D N‐graphdiyne (NGDY) nanosheets 290 cytochrome P450 20, 47, 204, 206, 207, 326 N‐(4‐hydroxybenzoyl)aminohexyl agarose phenylacetone 47, 199, 202, 203, 208, 322 affinity matrix 12–13 polycyclic ketone 21 nickel Raney‐catalysed hydrogenation 383 styrene 19, 199, 204–205, 331, 381, Nicotiana tabacum double-bond reductase 388–389, 394 (NtDBR) 347 xylene 204 nicotinamide adenine dinucleotide monostearin 303 (NADH) 10, 12, 80, 93, 107, 144, 181, monoterpenic alcohols 305 187, 275, 277, 292, 312, 321, 381, 449, montelukast 188, 436–439 454, 474

deGonzalo_bindex.indd 500 17-03-2021 20:34:28 Index 501

nicotinamide adenine dinucleotide/ bienzymatic linear cascades 365–367 nicotinamide adenine dinucleotide norbornadiene ruthenium complexes phosphate (NADH/NADPH) 449 (Rh[nbd]) 95 nicotinamide adenine dinucleotide phosphate norcoclaurine synthase (NCS) 167–168, (NADPH) 12, 107, 181, 184, 275, 312, 376, 390 321, 381, 474 norcoclaurine synthase‐catalysed Pictet– nicotinamide‐dependent Spengler reaction 390 dehydrogenases 332 norcoclaurine synthase D29TfNCS 376 nicotinamide‐dependent flavoproteins 336 norhygrine 365 NifL PAS domain 20 norsedaminone 365 Ni‐NTA affinity chromatography 19, 20, 21 nothofagin 227, 228, 229, 230, 232, 233, 235, Ni‐NTA‐sepharose 312 236, 237 nitrilases 468, 469, 481 nothofagin synthesis 227, 229, 230, 232, nitrile‐triacetic acid (NTA) 19, 20, 21, 312 233, 235, 236 4‐nitrobenzaldehyde 130–134 Novozym• 435 302, 304, 305, 306, 307, 309, 5‐nitrobenzisoxazole 40 310, 474 nitrogen‐doped carbon nanodot (N‐CD) 340 Novozymes 474 p‐nitrophenyl‐2‐phenylpropanoate 45 catalyzed transesterification 264–265 Nocardia iowensis (NiCAR) 378 N‐protected α‐amino γ‐butyrolactone 415 nonane‐2,6‐dione 375 nucleophilic attack 46, 70, 122, 133, non‐aqueous media 145, 198 advantages 248 nucleoside diphosphate (NDP)‐sugar 225 bio‐based liquids nylon‐6 monomer 392

CO2‐expanded 264–265 CPME 261–262 o MeTHF 260–261 Ochrobactrum anthropi amine transaminase potential application for 262 (OaATA) 385 disadvantages 248 oct‐7‐yn‐1‐ol 364 enzymatic activity 251–252 Old Yellow Enzymes (OYEs) 191–194, 196, enzyme immobilization 253–254 198, 210, 374 enzyme preparation 254–255 olefin reduction 336–342 inactivation of enzymes 252 one‐pot megaprimer PCR 37 ionic liquids (ILs) 247, 250 one‐pot multienzymatic liquid CO2 262–263 transformations 362 micro‐aqueous system 258–259 one‐pot one‐enzyme oxidative Pictet– NADES 265 Spengler approach, organic solvents 247–248 deracemisation 151 pressurized gas 250 one pot reactions 92, 348 protein engineering 255–256 Ophiorrhiza pumila strictosidine synthase solvent‐free system 256–258 (OpSTR) 377 tolerant enzymes or host cells 252–253 Oppenauer oxidation 106 non‐chiral amines 363 optically active benzylamines 369 non‐homologous recombination 35 optically active gamma‐butyrolactones 380 non‐stereoselective bienzymatic optically active vicinal diols 379 transformations optically pure amines 306 amine synthesis 363–365 organic compound synthesis 377–383

deGonzalo_bindex.indd 501 17-03-2021 20:34:28 502 Index

organic dyes 319, 338, 345 2‐oxohexanedioic acid 385 organic‐inorganic hybrid nanoflower 254 oxygenations organic molecular photosensitizers 282–285 alkenes epoxidation 204–206 organic semiconductors 288–290 BVMOs 198–204, 210–211 organic solvent‐tolerant organisms 252 OYE 210 organic synthesis hydrolases 118–122 p reactions 37 palladium catalysis 409 organo‐ and biocatalysis 320, 415 pancreatic porcine lipase (PPL) 118–119, organo‐ and photocatalysis 320 125–126, 128–131, 131, 304 organocatalytic oxidation 415–417, 424 pancreatic porcine lipase type II (PPL‐ organocatalytic reaction with a II) 116, 131, 135–136 biotransformation 413–418 (R)‐pantolactone 414 Oriental Yeast 482 para‐nitrophenyl esters OSCARR methodology (One‐pot Simple spectrophotometrically 36 methodology for CAssette P450 BM3 variants 384 Randomization and Pd‐catalyzed Heck reaction 411, 424 Recombination) 37 PEG diester 306–307 osmotic shock 4 Penicillin G acylase (PGA) 65 O2‐tolerant deazaflavin 337 Penicillium simplicissimum 6, 10 4‐oxalocrotonate tautomerase (4‐OT) 117 pentaerythritol tetranitrate reductase 339 oxidases 8–9 pentamethylcyclopentadienyl rhodium amine 149–152 bipyridine complex [Cp*Rh(bpy) 2+ monoamine 172 (H2O)] 276, 334 6, 275, 467 Perkin condensation of C=C bonds reduction 2′‐chlorobenzaldehyde 166 enzymes 193 perovskites 319–320 enzymes 144 peroxidases 6, 8–9, 17, 79–80, 96, 207, 254, OYEs mechanism 191–192 367, 471, 482 enantiopure molecules 181–183 peroxycarboxylic acids 115, 116, 126 heteroatom oxidation peroxygenase‐catalyzed oxyfunctionalization Baeyer–Villiger oxidation reaction 324 reactions 206–208 peroxygenases 183, 207–209, 324–325, nicotinamide cofactor 183 349, 351 oxygenations 198–204 perylene diimide 290 recombinant enzymes 184 PETase (PET‐digesting enzyme) 47 reduction of C=O bonds P450 fatty acid decarboxylase 327 ADH 185 Phage‐assisted continuous evolution Aldo‐keto reductases (AKR) 184 (PACE) 35 long‐chain dehydrogenase/reductases pharmaceutical industry 3 (LDR) 184 (R)‐biphenylalanine 442 medium‐chain dehydrogenase/ boceprevir 439–442 reductases (MDR) 184 environmental aspects 454 NAD(P)H‐regeneration strategies 183 enzyme release testing 456–457 SDR 184 equipment cleaning 455–456

deGonzalo_bindex.indd 502 17-03-2021 20:34:28 Index 503

equipment utilization and throughput (R)‐1‐phenylethyl propionate 15 time 455 (S)‐phenylglycidol 390 esomeprazole 435–436 (S)‐phenylglycine 395 health 453 d‐phenylglycines 393, 394 identification of the suitable enzyme 443 1‐phenylpentane‐1,4‐dione 376 impurities 446–450 (S)‐2‐phenylpiperidine 391 montelukast 436–439 1‐phenylpropane‐1,2‐diol 259, 377–378 pregabalin 431–432 1‐phenylpropane‐1,2‐diol stereoisomers 378 process development 443–445 (S)‐phenylpropan‐2‐ol 369 process safety 453–454 phenylpropanolamines 167, 390 route of administration 451 1‐phenylprop‐2‐en‐1‐ol 382 sitagliptin 433–435 1‐phenylprop‐2‐yn‐1‐ol 382 transport and storage 457–458 Phenyl Sepharose column 6–7 type of expression system 451 phloxine B 338, 345 types of biocatalysts 450 pH memory 251 vernakalant 432–433 phosphane‐free palladium catalyst 410 phase junction 280 phosphine‐free perfluoro‐tagged palladium pH‐dependent inactivation 36 nanoparticle 410 phenolic acid decarboxylase (PAD) 98, 100, phosphite dehydrogenase 21, 276 101, 106, 388–389, 394 photo‐ and biocatalysis 320 phenylacetaldehyde 167, 388, 390 photobiocatalysis phenylacetaldehyde reductase (PAR) 388–389 alkane hydroxylation 322–326 phenylacetone monooxygenase (PAMO) 47, Baeyer–Villiger (BV) oxidation 321–322 199, 202, 203, 208, 322 carbonyl reduction 332–336 phenylacrylic acid decarboxylase combination of photooxidation and (PAD) 388, 394 enzymatic transformation 348–351 l‐phenylalanine 158, 388, 389, 394 deacetoxylation 347–348 phenylalanine aminomutase decarboxylation 327–330 (PAM) 162–163, 165, 386 dehalogenation 345–347 phenylalanine ammonia lyase epoxidations 330–331 (PAL) 162–163, 165–166, 386, imine reduction 342–344 388–389, 394 O‐dealkylation 326–327 phenylalanine self‐assembled peptide olefin reduction 336–342 nanotubes 283 reductive amination 344–345 4‐phenylbutan‐2‐amine 374 photocatalytic NADH regeneration 278–292 (R)‐4‐phenylbutan‐2‐amine 11 aspects of measuring 281–282 (S)‐4‐phenylbutan‐2‐amine 371 expectations 290–291 4‐phenylbutan‐2‐ol 368 inorganic semiconductors 285–287 2‐phenyletanol 389 nature photosensitizers 282 1‐phenylethane‐1,2‐diol 374 organic molecular (R)‐1‐phenylethane‐1,2‐diol 394 photosensitizers 282–285 2‐phenylethanol 387–388 organic semiconductors 288–290 rac‐1‐phenylethylamine 306–308 processes and mechanism associated (S)‐1‐phenylethylamine with cellulose with 279–281 immobilized transaminase 312 recycling 292

deGonzalo_bindex.indd 503 17-03-2021 20:34:29 504 Index

photoredox system 322, 324 Prelog’s rule 45, 185 photosensitizers P680 282 Prelog‐type alcohols 185 photosensitizers P700 282 pressurized gas 247–250, 253, 264, 267 Pichia pastoris alcohol oxidase primary amine 119, 126, 145, 156, 167, (PpAOX) 378, 451 364, 472 pickering emulsions 98–100 process safety 430, 442, 453–454 Pictet–Spenglerases 173–174 proline‐derived organocatalyst 413 catalytic mechanism 167 promiscuity (R)‐harmicine 168–169 catalytic 116–117 norcoclaurine synthase 167 hydrolases strictosidine synthase 167 aldol reaction 130–134 Pictet–Spengler reaction 167, 169, 173–174, catalytic promiscuity 122–130 390, 420 esterases 117–118 plastocyanin (PC) 282 lipases 122 platinum nanoparticles 283 organic synthesis 118–122 Pleurotus eryngii 20 proteases 118 polyacrylamide 5, 66 rac‐1,2‐propanediol 309 polycyclic ketone monooxygenase propan‐2‐ol 104, 266, 309, 369 (PockeMO) 21 propanol‐rinsed enzyme preparation polydimethylsiloxane (PDMS) (PREP) 254 thimbles 103–105 propargylamine 364 polyethylene terephthalate (PET) 47 propargylic alcohols 382 polymerase chain reaction propiophenone 266, 382 (PCR) 35, 37, 448 proteases 3, 5, 13, 20, 39, 46, 91, 95, polymersomes 101–103 117–119, 131, 145–146, 262, 305, 310, polymethacrylate 66 439, 453, 468, 474, 476–478, 480 porcine pancreas lipase type II protein‐based stains 118 (PPL‐II) 135–136 protein cage 95 porcine pancreatic lipase (PPL) 129–130 protein complex photosystem I (PS I) 282 porcine pancreas (PPL) 118 protein complex photosystem II (PS II) 282 porous carriers Protein Data Bank (PDB) 38, 40, 42, 49, commercial 68 186, 193 definition 66 protein design automation (PDA) 38 dimensions 67–68 protein engineering 36, 47–50, 63–64, 82, geometry 116, 155–156, 158–159, 162–163, 186, beads 67 188, 197–198, 201, 247, 255–256, 267, monoliths 67 374, 425, 459, 475, 481 inorganic materials 66–67 techniques 374 membranes 67 protein immobilization organic materials 66 affinity immobilization 70 porous membranes 67, 101 apparent kinetic parameters 76–77 porphyrin π radical ferryl biocatalyst stability 77–78 intermediate 323 carriers nature 64 porphyrins 283–284, 323, 335 challenges and opportunities 79–81 pregabalin 431–432 chemical and geometrical congruence 65

deGonzalo_bindex.indd 504 17-03-2021 20:34:29 Index 505

covalent binding 70 Pseudomonas species styrene monooxygenase cross‐linking 70 (Fus‐SMO) 390 entrapment/encapsulation 70 Pseudomonas stutzeri lipase (PSL) 261, 310 enzymatic solution preparation 71 PTDH‐PockeMO protein 21 enzyme spatial organization 65–66 pure 4‐hydroxybenzoate 3‐hydroxylase GlyDH 73 (PHBH) 10 heterogeneous biocatalysts 74, 76 Purified ADH from Codex• immobilization chemistry 64 Screening Kit 266 parameters Purolite Ltd 68 expressed activity/apparent putidaredoxin‐NAD+ reductase (PDR) 334 activity 72–73 pyridoxal 5′‐phosphate (PLP) 416, 433, 454 immobilization yield (IY) 72 dependent enzymes 11 immobilized biocatalyst (SA) 73 Pyrococcus furiosus 19, 95 physical adsorption 69 1‐pyrrolines 342–343 porous carriers pyruvate aldolase (PyrAL) 372 commercial 68 pyruvate decarboxylase (PDC) 153, 379 definition 66 372–373 dimensions 67–68 geometry 67 q inorganic materials 66–67 Q‐Sepharose ion‐exchange membranes 67 chromatography 7 monoliths 67 Q‐Sepharose ion exchanger 21 organic materials 66 quantitative structure activity relationship protein attachment 65 (QSAR) algorithm 38 protein orientation 64–65 quantum dots (QDs) 289, 319, 320, reversible and irreversible 332–333, 338–339 immobilization 69 nanocrystals 285

soluble enzyme stability 71 quantum dots@flake g‐C3N4 isotype protein stability 42–43, 361, 475 heterojunctions 289 PROtein Structure Activity Relationship quantum dots@flake graphitic carbon nitride

(ProSAR) algorithm 38 (QDs@flake g‐C3N4) isotype proteolytic degradation 5 heterojunctions 289 Proteus mirabilis 385 quantum mechanical (QM) methods 40–41 Proteus myxofaciens 392 “Quick E” assay 36 Prozomix 351, 375, 474–475 Quick Quality Control (QCC) 35 Pseudomonas cepacia lipase (PSL)‐catalyzed transesterification 261 r Pseudomonas fluorescens lipase (PFL) 8, 10, rAaeUPO‐catalyzed hydroxylation 325 15, 17, 48 racemic α‐acetoxytetralones 347 catalyzed transesterification 263 racemic amino acid 386, 431 Pseudomonas fluorescens BAL racemic 2‐aminobutanoic acid 385 (PfBAL) 351, 377 racemic 1‐aminotetralin 149 Pseudomonas oleovorans 206 racemic 1‐arylalkanols 370 Pseudomonas putida (MorB) 94, 334, racemic benzylisoquinolines 371 335, 378 racemic cis‐4‐methyl‐2‐phenylpiperidine 391

deGonzalo_bindex.indd 505 17-03-2021 20:34:29 506 Index

racemic cyano diester 431 reductive amination 143–144, 155, 157–162, racemic in situ‐formed hexahydrofuro[2,3‐b] 172–173, 344–345, 348–349, 393 furan‐3‐ol 415 renewable catalysts 275 racemic 1,2‐isopropylidene glycerol 303, 304 renewable electric energy 276 racemic ketone 234–235, 433 residual activity 77, 90 racemic mandelic acid 393–394 Resindion Srl 68 racemic methylbenzylamine (rac‐MBA) 364 retro‐biosynthesis approach 48 racemic N‐Boc‐phenylalanine ethyl reversible covalent bonds 70 thioester 310–311 reversible immobilization 15, 64, 69–70 racemic phenyl alanine derivatives 385 Reynolds numbers 300 racemic sulfoxide 436 Rh‐catalyzed diazoester 424 racemic 1‐(trityloxy)propan‐2‐ol 309 Rhizomucor miehei (RM IM) 8 rac‐1,2‐propanediol 309 Rhizopus niveus lipase (RNL) 116, 131, rac‐1‐(trityloxy) propan‐2‐ol 309 134–136, 135 Ralstonia species alcohol dehydrogenase Rhizopus oryzae 387 (RasADH) 377 rhodamine G 319 RAndom CHImeragenesis on Transient Rhodococcus erythropolis DSM Templates (RACHITT) 35 43297 ADH 381 random mutagenesis approaches 34–35 rose bengal (RB) 319, 338, 345 RAndom MUtagenesis Strategy flowchart Rosetta‐guided protein stapling (RAMUS) 35 (R‐GPS) 256 rational enzyme design 34 Rosetta model 40 2+ calmodulin 43 [Ru(bpy)3] 319

enantiomerically pure synthesis 45–47 Ru(bpy)3Cl2 335–336, 344 II identification of tunnels 48–49 [Ru (bpy)2(4,4′‐(PO3H2)2bpy)]Br2 Kemp elimination 43–44 (RuP) 341–342 MD simulations 41 ruspolinone 365 metalloproteins 45 ruthenium‐catalyzed isomerization 266 molecular docking methods 41 protein stability 42–43 s QM/MM techniques 41 saccharose‐producing mutant 94 substrate scope 47–48 saturation mutagenesis 37, 39, 187 rational parametric design 39, 40 Saxagliptin 124–125 Rauvolfia serpentina strictosidine synthase SCHEMA 35 (RsSTR) 168–169 SCRATCHY 35 recombinant enzyme purification SDS‐PAGE 5, 6, 14, 446, 457 affinity chromatography with protein secologanin 168, 169, 377 tags 20–22 secondary α‐bromoamides 347 IMAC 18–20 Segniliparus rugosus 364 reconstructing evolutionary adaptive paths selectAZymesTM kits 468 (REAP) methods 38 selection techniques 36 reduced nicotinamide cofactor 332, 372 semi‐rational design 34 reductases 8–9, 155–162, 184, 347, 390, computational methods 38 392, 470 high‐throughput screening methods 37 reductive aminases (RedAms) 144, 155–162, sequence‐based enzyme engineering 38 365, 376 sequence‐based redesign 39

deGonzalo_bindex.indd 506 17-03-2021 20:34:29 Index 507

structure‐based enzyme redesign 37–38 (S)‐mandelate dehydrogenase structure‐based redesign 38–39 (SMDH) 389, 394 sequence‐based enzyme engineering 38 sodium cyanide (NaCN) 367 sequence‐based redesign 39 sodium dodecyl sulfate polyacrylamide gel Sequence Homology‐Independent Protein electrophoresis (SDS‐PAGE) 5–6, 14, RECombination (SHIPREC) 35 446, 457 Sequence‐Independent Site‐Directed Solanum tuberosum epoxide hydrolases Chimeragenesis (SISDC) 35 (StEH) 390 sequential cascade 90, 93 solar energy 278–280, 282–283, 285, 292 sequential chemoenzymatic one‐pot solubility tags 20–21 synthesis soluble epoxide hydrolase (sEH) 46 combining more than two solvent engineering 91–92, 232–233, 410 reactions 420–422 solvent tolerance 36 metal‐catalyzed reaction with a (S)‐specific oxidoreductase 381 biotransformation 408 Sphingobium yanoikuyae 186, 369 organocatalytic reaction with a Sphingomonas species HXN200 biotransformation 413–418 (SpEH) 390, 394 practical approaches 422–425 SpinChem reactor 378 reaction catalyzed by a heterogeneous SpinChem rotating bed reactor 103 biocatalyst with a chemocatalytic stabilization factor (SF) 79 transformation 419–420 staggered extension process (StEP) 35 reaction catalyzed by a heterogeneous stearic acid 303–304, 328 chemocatalyst with a stereocontrol biotransformation 418–419 dynamic kinetic resolution 197–198 serine‐histidine‐aspartate residues enzyme‐based approach 197 (Ser‐His‐Asp) 118 OYEs advantage 196 serine protease family 145 substrate‐based approach 196–197 Sertraline 307 stereoselective bienzymatic transformations Shewanella frigidimarina NCIMB400 341 amination of alcohols 368–371 short‐chain dehydrogenase/reductases amino acid synthesis 383–386 (SDR) 184, 192 amino alcohol synthesis 372–374 short‐chain esters 305 deracemisation of amines 371–372 Sigma–Aldrich 477–478 organic compound synthesis 377–383 silica nanoflowers (SNFs) 99–100 other synthesis 374–377 Silicibacter pomeroyi amine transaminase stereoselective KRED‐catalyzed carbonyl (SpATA) 366 reduction 349 silicone 66 stilbenes 97, 106 single electron transfer (SET) 322, 326, 330, Strem Chemicals, Inc. 478 336–345, 348 Streptomyces coelicolor 21, 369 single enzyme immobilization 92 Streptomyces maritimus (EncP) 386 sitagliptin 155, 433–435 strictosidine synthase (STR) 167–169, site‐saturation mutagenesis (SSM) 34, 37 173–174, 377 six‐membered α‐bromolactones 346 structure‐based enzyme redesign 37–38 size exclusion chromatography styrene monooxygenase (SMO) 19, 199, (SEC) 9–10, 17, 237 204–205, 331, 381, 388–389, 394 small ubiquitin modifier (SUMO) 20–21 (S)‐styrene oxide 394

deGonzalo_bindex.indd 507 17-03-2021 20:34:29 508 Index

styrene oxide isomerase (SOI) 388–389 Thermoanaerobium brockii 332 2‐substitued‐1‐pyrrolines 342 Thermocrispum municipale 2‐substituted N‐heterocycle alkaloids 365 cyclohexanone monooxygenase substrate coupling method 276 (TmCHMO) 20 Subtilisin Carlsberg (SC) 46, 254, 310 thermophilic Old Yellow Enzyme sugar component 225 (TOYE) 339 Sulfolobus solfataricus dihydroxyacid Thermothelomyces thermophila 20 dehydratase (SsDHAD) 105 Thermothelomyces thermophile 21

supercritical CO2 (scCO2) 250–251, 253, 310 Thermus scotoductus old yellow enzyme surface defects 280 (TsOYE) 338–340 Surface‐Enhanced Resonance Raman Thermus thermophilus proline dehydrogenase Scattering (SERRS) 36 (TtProDH) 11, 21–22 Suzuki coupling reaction 409–410, 424 thiophene‐modified double shell hollow

Suzuki–Miyaura cross‐coupling 105 g‐C3N4 nanosphere 289 Symbiobacterium thermophilum 385 thioredoxin (Trx) 20 syn‐ and anti‐aldols 24 three dimensional aromatic polymer synthetic biology 50, 231, 275, 292 (3DAP) 290 synthetic nicotinamide cofactor analogues thylakoid membrane 94, 282–283 (mNADHs) 340 thylakoids 94, 282–283 synthetic polymers 66 Ticagrelor 121–122

TiO2‐CdS nanotube film (NT‐film) 287 t total turnover number (TTN) 78–79, 208, Takabio 482 230, 233, 313, 432 tandem/domino reaction 362 Toyobo Co., Ltd. 482–483 tea‐bag synthetic technology 103–104 Toyobo Enzymes 483 telescoping 90 traditional enzyme purification (S)‐tembamide 383 ammonium sulfate fractionation 6–7 N‐terminal MBP solubility tag 21 bio‐affinity chromatography 11–14 tertiary enantioenriched (R)‐amine 344 cell‐free extract 5 (S)‐6,8,13,13a‐tetrahydro‐5H‐ cleared cell extract 4 isoquinolino[3,2‐a]isoquinoline‐ gel‐filtration 9–11 2,3,10,11‐ HAP 15–17 tetraol 376 HIC 14–15 1,2,3,4‐tetrahydroisoquinolines 390 3‐hydroxyphenylacetate 6‐hydroxylase (1S,3S,4R)‐1,2,3,4‐ from Flavobacterium JS‐7 17–18 tetrahydroisoquinolines 391 IEC 7–9 2,2,6,6‐tetramethylpiperidine‐1‐oxyl inactivation and/or aggregation 5 (TEMPO) 381, 415 microbial cells 4 Thalictrum flavum 167, 169 SDS‐PAGE gel 5–6 theoretical enzyme or theozyme 40 separation methods 5 Thermoanaerobacter ethanolicus alcohol theoretical example 4 dehydrogenase (TesADH) 45, 253, Trametes versicolor laccase (LTv) 369 258, 368–369 transaminase‐catalyzed amine Thermoanaerobacter pseudoethanolicus 339 synthesis 410 Thermoanaerobacter species 380 transaminases 144, 384

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asymmetric synthesis from prochiral u ketone 155 ubiquinone 275 kinetic resolution and UDP‐glucose 228–230, 235 deracemisation 153–155 Ugi reaction 115, 126 ping‐pong bi‐bi mechanism 152 ultra high‐throughput screening and practical approach 153 selection 35–36 pyridoxamine 152 α,β‐unsaturated acetophenones 336 reversible catalytic cycle 152 α,β‐unsaturated aldehydes 379 ωTAs 152 α,β‐unsaturated imines 375 α‐ or β‐transaminases 152 α,β‐unsaturated ketone 351, 381 ω‐transaminases 11, 152, 172, 363, 468 uridine 5′‐diphospho (UDP)‐glucose 228 transesterification reactions 46, 116, 118, 124–126, 128, 248, 261–264, 304–305, v 330, 415 vanillyl alcohol oxidase 6, 10, 17, 19 12, 24, 156, 361, 467, 474 vernakalant 432–433 467 Vibrio fluvialis (VfATA) 364 triacylglycerols (TG) 64, 122 virus capsids 95–96 lipases 116 volatile sulfur compounds (VSCs) 351 triazine‐linked 4′‐difluoro‐4‐bora‐3a,4a‐ diaza‐s‐indacene (BODIPY) 335, 364 w tricarboxylic acid cycle 94 Wacker oxidation of styrene 104 triethanolamine (TEOA) 188, 259, 280–281, W110A/G198D variant 368 283, 287, 292, 324, 326–327, 334–335, ‐N,N‐dimethylformamide (DMF) 338–340, 345, 434, 437 reaction media 410 2,2,2‐trifluoroacetophenone 253 water‐soluble palladium nanoparticles 409 α,α,α‐trifluorotoluene 418 water‐soluble palladium‐TSPP‐tris(3‐ (3S,4R)‐1,3,4‐trihydroxy‐5‐ sulfonatophenyl)phosphine phenylpentan‐2‐one 378 hydrate 410 tris(hydroxymethyl)aminomethane (Tris) 71 whole cells 3, 63, 89, 103, 157, 160, 166, trisubstituted tetrahydroisoquinolines 390 170, 184, 204, 206–207, 257–261, 266, 1,3,4‐trisubstituted 343, 377, 385, 391, 449–450, 455, tetrahydroisoquinolines 420 468, 484 (S)‐trolline 169 Worthington Biochemical Corp. 479

tryptamine 151, 168, 169, 173 WS2/g‐C3N4 heterojunction 290 tryptophan (Trp) 448 tubular molecular photosensitizer 283 x turnover frequency 283, 285, 322 X‐Cube (ThalesNano) system 303 turnover number 14, 257, 276, 322 xylanases 476 two‐dimensional sp2‐carbon COF xylene monooxygenase 204 (TP‐COF) 290 tyrosine (Tyr) 70, 156, 165, 192–193, 283, z 348, 384, 392, 448 zinc porphyrins (ZnDPEG) 283 tyrosine aminomutase (TAM) 165 zinc porphyrins (Zn‐porphyrins) 283 l‐tyrosine derivatives 383–384 zinc sulfide [ZnS] 285 Tyr‐ZnDPEG 283 Z‐scheme 282

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