Arthrobacter Nicotinovorans Pao1 a Tool to Produce Neuroactive Compounds

Total Page:16

File Type:pdf, Size:1020Kb

Arthrobacter Nicotinovorans Pao1 a Tool to Produce Neuroactive Compounds Arthrobacter nicotinovorans pAO1 a tool to produce neuroactive compounds Marius Mihășan, PhD Faculty of Biology Alexandru Ioan Cuza University of Iaşi, Romania E-mail: [email protected] A bit about my home country Romania Alexandru Ioan Cuza University of Iasi Area: 92,043 sq mi Population: 20,121,641 Transylvania Chemistry Biology Lazăr Edeleanu Microbiology: Victor Babeș the first to synthesize amphetamine more than 50 types of bacteria Vintilă Ciocâlteu Bio speleology: Emil Racoviță co-developed the Folin-Ciocalteu reagent the first to study the arctic life Nicolae Teclu Cell Biology: Emil Palade the Teclu burner the most influential cell biologist ever 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 2 / 27 Alexandru Ioan Cuza University of Iaşi Facts and figures ü The oldest Romanian university ü Diplomas recognized all over Europe Sciences Social Sciences & Humanities ü15 departments ü Biology ü Economics and Business Administration ü Chemistry ü History ü 93 Bachelor programs ü Computer Science ü Law ü Geography and Geology ü Letters ü Mathematics ü Orthodox Theology ü 176 Master programs ü Physics ü Philosophy and Social – Political Sciences ü Physical Education and Sports ü 26 PhD programs ü Psychology and Education Sciences ü Roman – Catholic Theology ü Center for European Studies 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 3 / 27 Department of Biology Bulevardul Carol I nr. 20A, Iaşi, Romania, 700505 Tel.:+40(0)232201072 Fax: 40(0)232201472 www.bio.uaic.ro Founded in 1948 ü 758 students: • 20 PhD students ü46 full-time faculty members ü 16 technicians and administrative staff 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 4 / 27 Programs of Study Biology BACHELOR Biochemistry semesters Environmental science Molecular genetics MASTER Biology Cellular and microbial biotech. Biodiversity Conservation Environment Counceling PhD 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 5 / 27 Study Programs Why I am in Potsdam? Sponsor: U.S. Department of State Romanian-U.S. Fulbright Commission Exchange Visitor Program Number G-1-00005 • Observe and learn the dynamics of a research group here in US • Attend lectures and understand the US academic system • Identify all the nicotine-induced proteins in Arthrobacter nicotinovorans by means of mass-spectrometry 6 months in Darie’s Biochemistry & Proteomics Group Department of Chemistry & Biomolecular Science, Clarkson University 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 6 / 27 Nicotine and nicotine-containing waste Nicotine • Produced by the tobacco plant to prevent consumption by herbivores • Responsible for smoking addiction - by releasing dopamine • Potentially lethal to humans (LD50 0.5 – 1.0 mg/kg) • Improves cognition, alertness, memory Nicotiana tabacum nAChRs - Nicotine acetylcholine receptors ligand-gated ion channel superfamily of neurotransmitter receptors Nicotine is a lead compound used for developing drugs for cognitive dysfunctions Levin ED and Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr DrugTargets CNS Neurol Disord. 2002;1(4):423-31. Taly et. all. Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system Nat. Rev. Drug Discov.2009, 8, 733-750. 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 7 / 27 Nicotine and nicotine-containing waste Tobacco industry produces 300 000 tons of non- recyclable nicotine-containing waste, 18 g nicotine/per kg • According to EPA the waste is Toxic Release Inventory (TRI) chemicals • According to the European Union Regulations (EUR) - “toxic and hazardous”(when nicotine content is over 0.05% w/w) Production in Country or region thousands of tons World 7176 China 2995 Brazil 862 GHS06 GHS09 India 720 United States 397 This waste is simply discarded in the environment European Union 262 According to FAOSTAT data, 2014 Why not using this waste to produce nicotine-based chemicals and drugs? Novotny TE et al. The environmental and health impacts of tobacco agriculture, cigarette manufacture and consumption. Bull World Health Organ.. 2015;93(12):877-880. 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 8 / 27 What is Arthrobacter nicotinovorans? Why are we still studying bacteria? Arthrobacter Photo by: T. Tamura, T. Nishii & K. Hatano Arthrobacter nicotinovorans can grow on media containing up Microorganism isolated from to 6 g/L nicotine tobacco cultivated soil Dana Krempels, Introduction to Evolution, http://www.bio.miami.edu/dana/107/107F10_5print.html 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 9 / 27 Arthrobacter nicotinovorans and nicotine degradation Brandsch group, Albert Ludwigs University of Freiburg, Germany isolation and sequencing of the plasmid Arthrobacter Oxydans 1 – pAO1 Nicotine metabolism Carbohydrate catabolism Transposons and insertion elements Plasmid replication, partition and conjugation; 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 10 / 27 The nic gene cluster on pAO1 kdhS ndhM transp coxF coxD coxG pkc mobA coxE nit dhph kdhL ponH kdhM 6hlno ndhLndhS IS1473 II TRu TRd I Tn554 nepA perm transp Tn554 nbor mao sad nepB folD abo purU 49500 pmfR III IV moaD moeA modA modC lacI hdno trsp moaA moaC modB Nicotine catabolism, experimental Nicotine catabolism, putative hdnoR V VI 118000 Transcription factors, experimental or putative Putative ORFs, no function Transposons and insertion elements 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 11 / 27 The nicotine break-down pathway in A. nicotinovorans I VI II IV III Mihasan M. Arthrobacter nicotinovorans – new insights into its metabolism, molecular genetics and biotechnological applications, Habilitation thesis, Iasi, 2016 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 12 / 27 Upper nicotine pathway in A. nicotinovorans Nicotine 6-OH, L-Nicotine oxidase dehydrogenase 6-OH, D-Nicotine oxidase Nicotine 6-OH NicotineN 6-OH, CH3-Myosmine 6HNic Ketone dehydrogenase 6-OH PseudooxinicotineN 2,6-diOH Pseudooxinicotine N I VI NDH – nicotine dehydrogenase 6-OH L–Nicotine oxidase KDH – ketone dehydrogenase and heterotrimeric (αβγ)2 enzymes FAD , MCD and FeS clusters 6-OH D–Nicotine oxidase absolute stereospecificity, genetically and structurally unrelated flavoenzymes V Kachalova et al., 2010, J Molec Biol., 396(3):785-799 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 13 / 27 The nicotine break-down pathway in A. nicotinovorans I VI II IV III 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 14 / 27 Pyridine ring metabolism in A. nicotinovorans II 2,6-diOH PseudooxinicotineN An α/β fold C-C bond hydrolase 2,6-diOH Pseudooxinicotine hydrolase no sequence similarity to known bacterial meta-cleavage c-c bond hydrolases Methyl-γ-aminobutyricN acid 2,6-diOHN Pyridine MGABA 2,6-diOH Pyridine hydroxylase 2,3,6-triOHN Pyridine Nicotine-blue Oxidoreductase Schleberger et al., 2006, J Molec Biol., 367(2):409-418 Mihasan et al. 2007 Appl Environ Microbiol 73 (8), 2479-2485. 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 15 / 27 The nicotine break-down pathway in A. nicotinovorans I VI II IV III 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 16 / 27 Side chain metabolism in A. nicotinovorans Methyl-γ-aminobutyric acid Oxidoreductase Amine IV Oxidase Genetic or γ-aminobutyric acid allosteric Monoamine regulation probably Oxidase switches between the two variants III Dehydrogenase 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 17 / 27 Blank spots in nicotine metabolic pathway in A. nicotinovorans 1. Is Nicotine-Blue (NB) the final product of the pathway? A. Nicotine-blue is consumed in old cultures A pyridine ring cleaving enzyme must exist Unknown enzyme? Razavn B., B.Sc Doina G. B.Sc Chromosomal gene? Andreea A., M.Sc B. A ω-amidase for α-ketoglutaramate is part of the nic-gene cluster 2,3,6-triOH 3,6-diOH α-keto- Pyridine 2-Pyridinon glutamarate Flexible targeted docking ω-amidase Cobzaru, C., et al. (2011) Research in Microbiology, 162(3), 285–91. Petra G. Nicotine-blue α-keto-glutarate 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 18 / 27 Blank spots in nicotine metabolic pathway of A. nicotinovorans 2. How is nicotine transported across the cell membrane? L-nicotine uptake in A. nicotinovorans: facilitated diffusion • Dependent on nicotine degradation but not on pAO1 driven by the nicotine gradient due • Energy-independent to its intracellular degradation • Saturable with a K(m) of 6.2 microM and a V(max) of => 0.70 micromol/ min/mg protein) by a unknown Ganas & Brandsch, 2009, Microbiology, 155: 1866–77 chromosomal permease 3. Several other bacteria have the nic gene cluster, but not a functional nicotine catabolism pAO1 AK-YN10 99% sequence identity between key nic-genes in A. nicotinovorans and AK-YN10. Same nic-genes but no Razvan B, M.Sc Victor B., M.Sc. France nicotine metabolism AK-YN10 contains a plasmid Some chromosomal genes must be directly/indirectly involved in nic catabolism 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 19 / 27 Potential applications of the nic-pathway 1. Decontamination of nicotine-containing waste, soil and water from tobacco industry 2. Engineering the nic-pathway for the production of value-added chemicals 5/6/17 Arthrobacter nicotinovorans pAO1 as a tool to produce neuroactive compounds Slide 20 / 27 6-hydroxy-L-nicotine – a neuroactive agent? Nicotine improves memory by binding to nAChRs subtypes α4β2 Murray and Abeles, Aging & Mental Health. 2002, 6, 129–138. Could nicotine derivatives from Arthrobacter also bind nAChR’s? In silico - Targeted docking – rigid receptor subunits A and B from PDB ID 1UW6 - targeted region - a cube of aprox.
Recommended publications
  • Functional Identification of a Novel Gene, Moae, for 3
    www.nature.com/scientificreports OPEN Functional Identification of a Novel Gene, moaE, for 3-Succinoylpyridine Degradation in Received: 29 May 2015 Accepted: 28 July 2015 Pseudomonas putida S16 Published: 25 August 2015 Yi Jiang1,2, Hongzhi Tang1,2, Geng Wu1,2 & Ping Xu1,2 Microbial degradation of N-heterocyclic compounds, including xanthine, quinoline, nicotinate, and nicotine, frequently requires molybdenum hydroxylases. The intramolecular electron transfer chain of molybdenum hydroxylases consists of a molybdenum cofactor, two distinct [2Fe-2S] clusters, and flavin adenine dinucleotide. 3-Succinoylpyridine monooxygenase (Spm), responsible for the transformation from 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine, is a crucial enzyme in the pyrrolidine pathway of nicotine degradation in Pseudomonas. Our previous work revealed that the heterotrimeric enzyme (SpmA, SpmB, and SpmC) requires molybdopterin cytosine dinucleotide as a cofactor for their activities. In this study, we knocked out four genes, including PPS_1556, PPS_2936, PPS_4063, and PPS_4397, and found that a novel gene, PPS_4397 encoding moaE, is necessary for molybdopterin cytosine dinucleotide biosynthesis. Resting cell reactions of the moaE deletion mutant incubated with 3 g l−1 nicotine at 30 °C resulted in accumulation of 3-succinoylpyridine, and the strain complemented by the moaE gene regained the ability to convert 3-succinoylpyridine. In addition, reverse transcription-quantitative polymerase chain reaction analysis indicated that the transcriptional levels of the genes of moaE, spmA, and spmC of Pseudomonas putida S16 were distinctly higher when grown in nicotine medium than in glycerol medium. Large quantities of tobacco wastes containing high concentration of nicotine are produced during tobacco manufacturing yearly1. Nicotine is well known to be harmful to human health and can cross biological membranes and blood-brain barrier easily2.
    [Show full text]
  • The Key to the Nornicotine Enantiomeric Composition in Tobacco Leaf
    University of Kentucky UKnowledge Theses and Dissertations--Plant and Soil Sciences Plant and Soil Sciences 2012 ENANTIOSELECTIVE DEMETHYLATION: THE KEY TO THE NORNICOTINE ENANTIOMERIC COMPOSITION IN TOBACCO LEAF Bin Cai University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cai, Bin, "ENANTIOSELECTIVE DEMETHYLATION: THE KEY TO THE NORNICOTINE ENANTIOMERIC COMPOSITION IN TOBACCO LEAF" (2012). Theses and Dissertations--Plant and Soil Sciences. 5. https://uknowledge.uky.edu/pss_etds/5 This Doctoral Dissertation is brought to you for free and open access by the Plant and Soil Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Plant and Soil Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained and attached hereto needed written permission statements(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine). I hereby grant to The University of Kentucky and its agents the non-exclusive license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless a preapproved embargo applies.
    [Show full text]
  • Structural Analysis of Quinoline 2-Oxidoreductase from Pseudomonas Putida 86
    Structural Analysis of Quinoline 2-Oxidoreductase from Pseudomonas putida 86 Structural and Biochemical Studies of Two Nus Family Proteins: NusB and NusA AR1-λN Complex NusA AR1-λN Complex NusB Quinoline 2-Oxidoreductase Irena Bonin Max-Planck-Institut für Biochemie Abteilung Strukturforschung D-82152 Martinsried, München 1 Max-Planck-Institut für Biochemie Abteilung Strukturforschung Structural Analysis of Quinoline 2-Oxidoreductase from Pseudomonas putida 86 Structural and Biochemical Studies of Two Nus Family Proteins: NusB and NusA AR1-λN Complex Irena Bonin Vollständiger Abdruck der von der Fakultät für Chemie der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. St. J. Glaser Prüfer der Dissertation: 1. apl. Prof. Dr. Dr. h.c. R. Huber 2. Univ.-Prof. Dr. Dr. A. Bacher Die Dissertation wurde am 22.09.2004 bei der Technischen Universität München eingereicht und durch die Fakultät für Chemie am 11.11.2004 angenommen. 2 Ai miei genitori 3 ACKNOWLEDGEMENTS Acknowledgments The work, here presented, was carried out in the Abteilung für Strukturforschung at the Max-Planck-Institut für Biochemie, Martinsried bei München, under the supervision of Prof. Dr. Dr. h.c. Robert Huber. I would like to start thanking Prof. Dr. Robert Huber for giving me the opportunity to work in his department, his financial support, and for providing the necessary conditions for the success of my projects. To Dr. Markus C. Wahl who helped me in the initial struggle and promptly accepted to share his projects with me. A special thank goes to Dr. Holger Dobbek and Dr.
    [Show full text]
  • Arthrobacter Nicotinovorans Pao1 Why Do We Need Its Proteome?
    Arthrobacter nicotinovorans pAO1 Why do we need its proteome? Marius Mihășan, PhD. Faculty of Biology Alexandru Ioan Cuza University of Iaşi, Romania E-mail: [email protected] 4/2/17 Arthrobacter nicotinovorans - Why do we need its proteome? Slide 1 / 26 A bit about my home country Romania Alexandru Ioan Cuza University of Iasi Area: 92,043 sq mi Population: 20,121,641 Transylvania Flight history: Chemistry: Biology: Tr aian Vu ia Vintilă Ciocâlteu Victor Babeș first airplane to take off on its own power co-developed the Folin-Ciocalteu reagent more than 50 types of bacteria Physics: Costin Nenițescu Emil Racoviță Ştefan Procopiu many new classes of inorganic compounds founder of biospeleology the Bohr-Procopiu magneton Nicolae Teclu Emil Palade the Teclu burner Nobel Prize for contributions to cell biology 4/2/17 Arthrobacter nicotinovorans - Why do we need its proteome? Slide 2 / 26 Alexandru Ioan Cuza University of Iaşi Facts and figures ü The oldest Romanian university ü Diplomas recognized all over Europe Sciences Social Sciences & Humanities ü15 departments ü Biology ü Economics and Business Administration ü Chemistry ü History ü 93 Bachelor programs ü Computer Science ü Law ü Geography and Geology ü Letters ü Mathematics ü Orthodox Theology ü 176 Master programs ü Physics ü Philosophy and Social – Political Sciences ü Physical Education and Sports ü 26 PhD programs ü Psychology and Education Sciences ü Roman – Catholic Theology ü Center for European Studies 4/2/17 Arthrobacter nicotinovorans - Why do we need its proteome? Slide 3 / 26 Department of Biology Bulevardul Carol I nr. 20A, Iaşi, Romania, 700505 Tel.:+40(0)232201072 Fax: 40(0)232201472 www.bio.uaic.ro Founded in 1948 ü 758 students: • 20 PhD students ü46 full-time faculty members ü 16 technicians and administrative staff 4/2/17 Arthrobacter nicotinovorans - Why do we need its proteome? Slide 4 / 26 Programs of Study Biology BACHELOR Biochemistry semesters Environmental science Molecular genetics MASTER Biology Cellular and microbial biotech.
    [Show full text]
  • Proteomics Based Analysis of the Nicotine Catabolism In
    www.nature.com/scientificreports OPEN Proteomics based analysis of the nicotine catabolism in Paenarthrobacter nicotinovorans Received: 11 February 2018 Accepted: 24 October 2018 pAO1 Published: xx xx xxxx Marius Mihăşan 1,2, Cornelia Babii1, Roshanak Aslebagh2, Devika Channaveerappa2, Emmalyn Dupree2 & Costel C. Darie2 Paenarthrobacter nicotinovorans is a nicotine-degrading microorganism that shows a promising biotechnological potential for the production of compounds with industrial and pharmaceutical importance. Its ability to use nicotine was linked to the presence of the catabolic megaplasmid pAO1. Although extensive work has been performed on the molecular biology of nicotine degradation in this bacterium, only half of the genes putatively involved have been experimentally linked to nicotine. In the current approach, we used nanoLC–MS/MS to identify a total of 801 proteins grouped in 511 non- redundant protein clusters when P. nicotinovorans was grown on citrate, nicotine and nicotine and citrate as the only carbon sources. The diferences in protein abundance showed that deamination is preferred when citrate is present. Several putative genes from the pAO1 megaplasmid have been shown to have a nicotine-dependent expression, including a hypothetical polyketide cyclase. We hypothesize that the enzyme would hydrolyze the N1-C6 bond from the pyridine ring with the formation of α-keto- glutaramate. Two chromosomally-encoded proteins, a malate dehydrogenase, and a D-3- phosphoglycerate dehydrogenase were shown to be strongly up-regulated when nicotine was the sole carbon source and could be related to the production the α-keto-glutarate. The data have been deposited to the ProteomeXchange with identifer PXD008756. Nicotine is the main alkaloid produced by the tobacco plant as an anti-herbivore chemical.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka Et Al
    US 2016O1861 68A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka et al. (43) Pub. Date: Jun. 30, 2016 (54) PROCESSES AND HOST CELLS FOR Related U.S. Application Data GENOME, PATHWAY. AND BIOMOLECULAR (60) Provisional application No. 61/938,933, filed on Feb. ENGINEERING 12, 2014, provisional application No. 61/935,265, - - - filed on Feb. 3, 2014, provisional application No. (71) Applicant: ENEVOLV, INC., Cambridge, MA (US) 61/883,131, filed on Sep. 26, 2013, provisional appli (72) Inventors: Jay H. Konieczka, Cambridge, MA cation No. 61/861,805, filed on Aug. 2, 2013. (US); James E. Spoonamore, Publication Classification Cambridge, MA (US); Ilan N. Wapinski, Cambridge, MA (US); (51) Int. Cl. Farren J. Isaacs, Cambridge, MA (US); CI2N 5/10 (2006.01) Gregory B. Foley, Cambridge, MA (US) CI2N 15/70 (2006.01) CI2N 5/8 (2006.01) (21) Appl. No.: 14/909, 184 (52) U.S. Cl. 1-1. CPC ............ CI2N 15/1082 (2013.01); C12N 15/81 (22) PCT Filed: Aug. 4, 2014 (2013.01); C12N 15/70 (2013.01) (86). PCT No.: PCT/US1.4/49649 (57) ABSTRACT S371 (c)(1), The present disclosure provides compositions and methods (2) Date: Feb. 1, 2016 for genomic engineering. Patent Application Publication Jun. 30, 2016 Sheet 1 of 4 US 2016/O186168 A1 Patent Application Publication Jun. 30, 2016 Sheet 2 of 4 US 2016/O186168 A1 &&&&3&&3&&**??*,º**)..,.: ××××××××××××××××××××-************************** Patent Application Publication Jun. 30, 2016 Sheet 3 of 4 US 2016/O186168 A1 No.vaegwzºkgwaewaeg Patent Application Publication Jun. 30, 2016 Sheet 4 of 4 US 2016/O186168 A1 US 2016/01 86168 A1 Jun.
    [Show full text]
  • 12) United States Patent (10
    US007635572B2 (12) UnitedO States Patent (10) Patent No.: US 7,635,572 B2 Zhou et al. (45) Date of Patent: Dec. 22, 2009 (54) METHODS FOR CONDUCTING ASSAYS FOR 5,506,121 A 4/1996 Skerra et al. ENZYME ACTIVITY ON PROTEIN 5,510,270 A 4/1996 Fodor et al. MICROARRAYS 5,512,492 A 4/1996 Herron et al. 5,516,635 A 5/1996 Ekins et al. (75) Inventors: Fang X. Zhou, New Haven, CT (US); 5,532,128 A 7/1996 Eggers Barry Schweitzer, Cheshire, CT (US) 5,538,897 A 7/1996 Yates, III et al. s s 5,541,070 A 7/1996 Kauvar (73) Assignee: Life Technologies Corporation, .. S.E. al Carlsbad, CA (US) 5,585,069 A 12/1996 Zanzucchi et al. 5,585,639 A 12/1996 Dorsel et al. (*) Notice: Subject to any disclaimer, the term of this 5,593,838 A 1/1997 Zanzucchi et al. patent is extended or adjusted under 35 5,605,662 A 2f1997 Heller et al. U.S.C. 154(b) by 0 days. 5,620,850 A 4/1997 Bamdad et al. 5,624,711 A 4/1997 Sundberg et al. (21) Appl. No.: 10/865,431 5,627,369 A 5/1997 Vestal et al. 5,629,213 A 5/1997 Kornguth et al. (22) Filed: Jun. 9, 2004 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2005/O118665 A1 Jun. 2, 2005 EP 596421 10, 1993 EP 0619321 12/1994 (51) Int. Cl. EP O664452 7, 1995 CI2O 1/50 (2006.01) EP O818467 1, 1998 (52) U.S.
    [Show full text]
  • Catabolism of 3-Hydroxypyridine by Ensifer Adhaerens HP1: a Novel Four-Component
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.08.898148; this version posted January 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Title: 2 Catabolism of 3-hydroxypyridine by Ensifer adhaerens HP1: a novel four-component 3 gene encoding 3-hydroxypyridine dehydrogenase HpdA catalyzes the first step of 4 biodegradation 5 6 Running title: 7 Microbial 3-hydroxypyridine degradation 8 9 Authors: 10 Haixia Wang a, Xiaoyu Wang a, Hao Ren a, Xuejun Wang a, Zhenmei Lu a# 11 12 a MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, 13 Zhejiang University, Hangzhou, China 14 15 #Address correspondence to Zhenmei Lu, [email protected] 16 17 18 19 20 21 22 23 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.01.08.898148; this version posted January 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 24 Abstract 25 3-Hydroxypyridine (3HP) is an important natural pyridine derivative. Ensifer 26 adhaerens HP1 can utilize 3HP as the sole source of carbon, nitrogen and energy to 27 grow. However, the genes responsible for the degradation of 3HP remain unknown. In 28 this study, we predicted that a gene cluster, designated 3hpd, may be responsible for the 29 degradation of 3HP. The initial hydroxylation of 3HP is catalyzed by a four-component 30 dehydrogenase (HpdA1A2A3A4), leading to the formation of 2,5-dihydroxypyridine 31 (2,5-DHP) in E.
    [Show full text]
  • Comparative Genomics Reveals Specific Genetic Architectures In
    ORIGINAL RESEARCH published: 31 October 2017 doi: 10.3389/fmicb.2017.02085 Comparative Genomics Reveals Specific Genetic Architectures in Nicotine Metabolism of Pseudomonas sp. JY-Q Jun Li 1, Shulan Qian 1, Lie Xiong 1, Chengyun Zhu 1, Ming Shu 2, Jie Wang 1, Yang Jiao 1, Houlong He 1, Fuming Zhang 3, Robert J. Linhardt 3 and Weihong Zhong 1* 1 Department of Applied Biology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China, 2 Technology Center, China Tobacco Zhejiang Industrial Co., Ltd., Hangzhou, China, 3 Departments of Chemical and Biological Engineering, Biological Science, Chemistry and Chemical Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States Microbial degradation of nicotine is an important process to control nicotine residues in the aqueous environment. In this study, a high active nicotine degradation strain named Pseudomonas sp. JY-Q was isolated from tobacco waste extract (TWE). This strain could completely degrade 5.0g l−1 nicotine in 24 h under optimal Edited by: Peng Luo, culture conditions, and it showed some tolerance even at higher concentrations Key Laboratory of Marginal Sea (10.0g l−1) of nicotine. The complete genome of JY-Q was sequenced to Geology, South China Sea Institute of Oceanology (CAS), China understand the mechanism by which JY-Q could degrade nicotine and tolerate Reviewed by: such high nicotine concentrations. Comparative genomic analysis indicated that Emmanuel F. Mongodin, JY-Q degrades nicotine through putative novel mechanisms. Two candidate University of Maryland, Baltimore, gene cluster duplications located separately at distant loci were predicted to be United States Jinxin Liu, responsible for nicotine degradation.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0266329 A1 Mathur Et Al
    US 2012026.6329A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0266329 A1 Mathur et al. (43) Pub. Date: Oct. 18, 2012 (54) NUCLEICACIDS AND PROTEINS AND CI2N 9/10 (2006.01) METHODS FOR MAKING AND USING THEMI CI2N 9/24 (2006.01) CI2N 9/02 (2006.01) (75) Inventors: Eric J. Mathur, Carlsbad, CA CI2N 9/06 (2006.01) (US); Cathy Chang, San Marcos, CI2P 2L/02 (2006.01) CA (US) CI2O I/04 (2006.01) CI2N 9/96 (2006.01) (73) Assignee: BP Corporation North America CI2N 5/82 (2006.01) Inc., Houston, TX (US) CI2N 15/53 (2006.01) CI2N IS/54 (2006.01) CI2N 15/57 2006.O1 (22) Filed: Feb. 20, 2012 CI2N IS/60 308: Related U.S. Application Data EN f :08: (62) Division of application No. 1 1/817,403, filed on May AOIH 5/00 (2006.01) 7, 2008, now Pat. No. 8,119,385, filed as application AOIH 5/10 (2006.01) No. PCT/US2006/007642 on Mar. 3, 2006. C07K I4/00 (2006.01) CI2N IS/II (2006.01) (60) Provisional application No. 60/658,984, filed on Mar. AOIH I/06 (2006.01) 4, 2005. CI2N 15/63 (2006.01) Publication Classification (52) U.S. Cl. ................... 800/293; 435/320.1; 435/252.3: 435/325; 435/254.11: 435/254.2:435/348; (51) Int. Cl. 435/419; 435/195; 435/196; 435/198: 435/233; CI2N 15/52 (2006.01) 435/201:435/232; 435/208; 435/227; 435/193; CI2N 15/85 (2006.01) 435/200; 435/189: 435/191: 435/69.1; 435/34; CI2N 5/86 (2006.01) 435/188:536/23.2; 435/468; 800/298; 800/320; CI2N 15/867 (2006.01) 800/317.2: 800/317.4: 800/320.3: 800/306; CI2N 5/864 (2006.01) 800/312 800/320.2: 800/317.3; 800/322; CI2N 5/8 (2006.01) 800/320.1; 530/350, 536/23.1: 800/278; 800/294 CI2N I/2 (2006.01) CI2N 5/10 (2006.01) (57) ABSTRACT CI2N L/15 (2006.01) CI2N I/19 (2006.01) The invention provides polypeptides, including enzymes, CI2N 9/14 (2006.01) structural proteins and binding proteins, polynucleotides CI2N 9/16 (2006.01) encoding these polypeptides, and methods of making and CI2N 9/20 (2006.01) using these polynucleotides and polypeptides.
    [Show full text]
  • All Enzymes in BRENDA™ the Comprehensive Enzyme Information System
    All enzymes in BRENDA™ The Comprehensive Enzyme Information System http://www.brenda-enzymes.org/index.php4?page=information/all_enzymes.php4 1.1.1.1 alcohol dehydrogenase 1.1.1.B1 D-arabitol-phosphate dehydrogenase 1.1.1.2 alcohol dehydrogenase (NADP+) 1.1.1.B3 (S)-specific secondary alcohol dehydrogenase 1.1.1.3 homoserine dehydrogenase 1.1.1.B4 (R)-specific secondary alcohol dehydrogenase 1.1.1.4 (R,R)-butanediol dehydrogenase 1.1.1.5 acetoin dehydrogenase 1.1.1.B5 NADP-retinol dehydrogenase 1.1.1.6 glycerol dehydrogenase 1.1.1.7 propanediol-phosphate dehydrogenase 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) 1.1.1.9 D-xylulose reductase 1.1.1.10 L-xylulose reductase 1.1.1.11 D-arabinitol 4-dehydrogenase 1.1.1.12 L-arabinitol 4-dehydrogenase 1.1.1.13 L-arabinitol 2-dehydrogenase 1.1.1.14 L-iditol 2-dehydrogenase 1.1.1.15 D-iditol 2-dehydrogenase 1.1.1.16 galactitol 2-dehydrogenase 1.1.1.17 mannitol-1-phosphate 5-dehydrogenase 1.1.1.18 inositol 2-dehydrogenase 1.1.1.19 glucuronate reductase 1.1.1.20 glucuronolactone reductase 1.1.1.21 aldehyde reductase 1.1.1.22 UDP-glucose 6-dehydrogenase 1.1.1.23 histidinol dehydrogenase 1.1.1.24 quinate dehydrogenase 1.1.1.25 shikimate dehydrogenase 1.1.1.26 glyoxylate reductase 1.1.1.27 L-lactate dehydrogenase 1.1.1.28 D-lactate dehydrogenase 1.1.1.29 glycerate dehydrogenase 1.1.1.30 3-hydroxybutyrate dehydrogenase 1.1.1.31 3-hydroxyisobutyrate dehydrogenase 1.1.1.32 mevaldate reductase 1.1.1.33 mevaldate reductase (NADPH) 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) 1.1.1.35 3-hydroxyacyl-CoA
    [Show full text]
  • Crystal Structure and Mechanism of CO Dehydrogenase, a Molybdo Iron-Sulfur Flavoprotein Containing S-Selanylcysteine
    Proc. Natl. Acad. Sci. USA Vol. 96, pp. 8884–8889, August 1999 Biochemistry Crystal structure and mechanism of CO dehydrogenase, a molybdo iron-sulfur flavoprotein containing S-selanylcysteine HOLGER DOBBEK*†,LOTHAR GREMER‡,ORTWIN MEYER‡, AND ROBERT HUBER* *Max-Planck-Institut fu¨r Biochemie, Abteilung Strukturforschung, D-82152 Martinsried, Germany; and ‡Lehrstuhl fu¨r Mikrobiologie, Universita¨t Bayreuth, D-95440 Bayreuth, Germany Contributed by Robert Huber, May 27, 1999 ABSTRACT CO dehydrogenase from the aerobic bacte- requires conformational changes of M introduced through the rium Oligotropha carboxidovorans catalyzes the oxidation of binding of M to LS (unpublished data). The S subunit harbors ؉ CO with H2O, yielding CO2, two electrons, and two H . Its two [2Fe–2S] centers, which are proximal and distal, respec- crystal structure in the air-oxidized form has been determined tively, to the molybdenum center. They are traditionally des- to 2.2 Å. The active site of the enzyme, which contains ignated type I and II according to spectroscopic properties, but molybdenum with three oxygen ligands, molybdopterin- the assignment is controversial (8, 9). Recent experiments with cytosine dinucleotide and S-selanylcysteine, delivers the elec- M subunit-depleted CO dehydrogenase preparations assign trons to an intramolecular electron transport chain composed the proximal center to type I and the distal to type II of two types of [2Fe–2S] clusters and flavin-adenine dinucle- (unpublished data). otide. CO dehydrogenase is composed of an 88.7-kDa molyb- CO dehydrogenase has been grouped into the sequence doprotein (L), a 30.2-kDa flavoprotein (M), and a 17.8-kDa family of molybdenum hydroxylases (10).
    [Show full text]