Module-Based Polyketide Synthase Engineering for de Novo Polyketide Biosynthesis

Nava, Alberto A.; Roberts, Jacob; Haushalter, Robert W.; Wang, Zilong; Keasling, Jay D.

doi:10.1021/acssynbio.3c00282

Title: Module-Based Polyketide Synthase Engineering for de Novo Polyketide Biosynthesis

Journal Article · 23 October 2023 · ACS Synthetic Biology

DOI: https://doi.org/10.1021/acssynbio.3c00282 · OSTI ID:2203299

Nava, Alberto A. ^[1]; Roberts, Jacob ^[1]; Haushalter, Robert W. ^[2]; Wang, Zilong ^[2];

^[3]

Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); University of California, Berkeley, CA (United States)
Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); University of California, Berkeley, CA (United States); Shenzhen Institutes for Advanced Technologies (China); Technical Univ. of Denmark, Lyngby (Denmark)

Polyketide retrobiosynthesis, where the biosynthetic pathway of a given polyketide can be reversibly engineered due to the colinearity of the polyketide synthase (PKS) structure and function, has the potential to produce millions of organic molecules. Mixing and matching modules from natural PKSs is one of the routes to produce many of these molecules. Evolutionary analysis of PKSs suggests that traditionally used module boundaries may not lead to the most productive hybrid PKSs and that new boundaries around and within the ketosynthase domain may be more active when constructing hybrid PKSs. As this is still a nascent area of research, the generality of these design principles based on existing engineering efforts remains inconclusive. Recent advances in structural modeling and synthetic biology present an opportunity to accelerate PKS engineering by re-evaluating insights gained from previous engineering efforts with cutting edge tools.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science (BSS); USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation. Bioenergy Technologies Office (BETO); US Air Force Office of Scientific Research (AFOSR); US Department of the Navy, Office of Naval Research (ONR); US Army Research Office (ARO); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; EE0008926; FA9550-21-F-0003; 2018253421

OSTI ID:: 2203299

Alternate ID(s):: OSTI ID: 2439719

Journal Information:: ACS Synthetic Biology, Vol. 12, Issue 11; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (81)

An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea Cortes, Jesus; Haydock, Stephen F.; Roberts, Gareth A. Nature, Vol. 348, Issue 6297 https://doi.org/10.1038/348176a0	journal	November 1990
Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology Weissman, Kira J. Natural Product Reports, Vol. 33, Issue 2 https://doi.org/10.1039/C5NP00109A	journal	January 2016
Biosynthesis of Polyketides in Streptomyces Risdian, Chandra; Mozef, Tjandrawati; Wink, Joachim Microorganisms, Vol. 7, Issue 5 https://doi.org/10.3390/microorganisms7050124	journal	May 2019
Activating Hybrid Modular Interfaces in Synthetic Polyketide Synthases by Cassette Replacement of Ketosynthase Domains Chandran, Sunil S.; Menzella, Hugo G.; Carney, John R. Chemistry & Biology, Vol. 13, Issue 5 https://doi.org/10.1016/j.chembiol.2006.02.011	journal	May 2006
Engineering the stambomycin modular polyketide synthase yields 37-membered mini-stambomycins Su, Li; Hôtel, Laurence; Paris, Cédric Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-27955-z	journal	January 2022
GRINS: Genetic elements that recode assembly-line polyketide synthases and accelerate their diversification Nivina, Aleksandra; Herrera Paredes, Sur; Fraser, Hunter B. Proceedings of the National Academy of Sciences, Vol. 118, Issue 26 https://doi.org/10.1073/pnas.2100751118	journal	June 2021
Substrate-bound structures of a ketoreductase from amphotericin modular polyketide synthase Liu, Chenguang; Yuan, Meijuan; Xu, Xu Journal of Structural Biology, Vol. 203, Issue 2 https://doi.org/10.1016/j.jsb.2018.04.001	journal	August 2018
Structural rearrangements of a polyketide synthase module during its catalytic cycle Whicher, Jonathan R.; Dutta, Somnath; Hansen, Douglas A. Nature, Vol. 510, Issue 7506 https://doi.org/10.1038/nature13409	journal	June 2014
Modular organization of genes required for complex polyketide biosynthesis Donadio, S.; Staver, M.; McAlpine, J. Science, Vol. 252, Issue 5006 https://doi.org/10.1126/science.2024119	journal	May 1991
De novo design and engineering of non-ribosomal peptide synthetases Bozhüyük, Kenan A. J.; Fleischhacker, Florian; Linck, Annabell Nature Chemistry, Vol. 10, Issue 3 https://doi.org/10.1038/nchem.2890	journal	December 2017
Crystal Structure of the Erythromycin Polyketide Synthase Dehydratase Keatinge-Clay, Adrian Journal of Molecular Biology, Vol. 384, Issue 4 https://doi.org/10.1016/j.jmb.2008.09.084	journal	December 2008
Structural Insight into the Reaction Mechanism of Ketosynthase-Like Decarboxylase in a Loading Module of Modular Polyketide Synthases Chisuga, Taichi; Nagai, Akira; Miyanaga, Akimasa ACS Chemical Biology, Vol. 17, Issue 1 https://doi.org/10.1021/acschembio.1c00856	journal	January 2022
Biosynthesis of polyketides by trans-AT polyketide synthases Helfrich, Eric J. N.; Piel, Jörn Natural Product Reports, Vol. 33, Issue 2 https://doi.org/10.1039/C5NP00125K	journal	January 2016
Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans Stinear, T. P.; Mve-Obiang, A.; Small, P. L. C. Proceedings of the National Academy of Sciences, Vol. 101, Issue 5 https://doi.org/10.1073/pnas.0305877101	journal	January 2004
Mapping the catalytic conformations of an assembly-line polyketide synthase module Cogan, Dillon P.; Zhang, Kaiming; Li, Xiuyuan Science, Vol. 374, Issue 6568 https://doi.org/10.1126/science.abi8358	journal	November 2021
Docking Domain Engineering in a Modular Polyketide Synthase and Its Impact on Structure and Function Buyachuihan, Lynn; Zhao, Yue; Schelhas, Christian ACS Chemical Biology, Vol. 18, Issue 7 https://doi.org/10.1021/acschembio.3c00074	journal	July 2023
Engineering a Polyketide Synthase for In Vitro Production of Adipic Acid Hagen, Andrew; Poust, Sean; Rond, Tristan de ACS Synthetic Biology, Vol. 5, Issue 1 https://doi.org/10.1021/acssynbio.5b00153	journal	November 2015
Accurate prediction of protein structures and interactions using a three-track neural network Baek, Minkyung; DiMaio, Frank; Anishchenko, Ivan Science, Vol. 373, Issue 6557 https://doi.org/10.1126/science.abj8754	journal	July 2021
The Lego-ization of polyketide biosynthesis Sherman, David H. Nature Biotechnology, Vol. 23, Issue 9 https://doi.org/10.1038/nbt0905-1083	journal	September 2005
Ketosynthase Domain Constrains the Design of Polyketide Synthases Klaus, Maja; Buyachuihan, Lynn; Grininger, Martin ACS Chemical Biology, Vol. 15, Issue 9 https://doi.org/10.1021/acschembio.0c00405	journal	August 2020
Evolution and Diversity of Assembly-Line Polyketide Synthases: Focus Review Nivina, Aleksandra; Yuet, Kai P.; Hsu, Jake Chemical Reviews, Vol. 119, Issue 24 https://doi.org/10.1021/acs.chemrev.9b00525	journal	December 2019
The Structure of Docking Domains in Modular Polyketide Synthases Broadhurst, R. William; Nietlispach, Daniel; Wheatcroft, Michael P. Chemistry & Biology, Vol. 10, Issue 8 https://doi.org/10.1016/S1074-5521(03)00156-X	journal	August 2003
Emulating evolutionary processes to morph aureothin-type modular polyketide synthases and associated oxygenases Peng, Huiyun; Ishida, Keishi; Sugimoto, Yuki Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11896-1	journal	September 2019
Structure and Mechanism of the 6-Deoxyerythronolide B Synthase Khosla, Chaitan; Tang, Yinyan; Chen, Alice Y. Annual Review of Biochemistry, Vol. 76, Issue 1 https://doi.org/10.1146/annurev.biochem.76.053105.093515	journal	June 2007
Protein complex prediction with AlphaFold-Multimer Evans, Richard; O???Neill, Michael; Pritzel, Alexander https://doi.org/10.1101/2021.10.04.463034	preprint	March 2022
Biosynthesis: Is it time to go retro? Bachmann, Brian O. Nature Chemical Biology, Vol. 6, Issue 6 https://doi.org/10.1038/nchembio.377	journal	June 2010
Highly accurate protein structure prediction with AlphaFold Jumper, John; Evans, Richard; Pritzel, Alexander Nature https://doi.org/10.1038/s41586-021-03819-2	journal	July 2021
The PSIPRED Protein Analysis Workbench: 20 years on Buchan, Daniel W. A.; Jones, David T. Nucleic Acids Research, Vol. 47, Issue W1 https://doi.org/10.1093/nar/gkz297	journal	April 2019
Clearing the Skies over Modular Polyketide Synthases Sherman, David H.; Smith, Janet L. ACS Chemical Biology, Vol. 1, Issue 8 https://doi.org/10.1021/cb600376r	journal	September 2006
Short-chain ketone production by engineered polyketide synthases in Streptomyces albus Yuzawa, Satoshi; Mirsiaghi, Mona; Jocic, Renee Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-07040-0	journal	November 2018
Robert Robinson Lecture. Retrosynthetic thinking—essentials and examples Corey, E. J. Chem. Soc. Rev., Vol. 17, Issue 0 https://doi.org/10.1039/CS9881700111	journal	January 1988
A Polyketide Synthase Acyltransferase Domain Structure Suggests a Recognition Mechanism for Its Hydroxymalonyl-Acyl Carrier Protein Substrate Park, Hyunjun; Kevany, Brian M.; Dyer, David H. PLoS ONE, Vol. 9, Issue 10 https://doi.org/10.1371/journal.pone.0110965	journal	October 2014
The 2.7-A crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase Tang, Y.; Kim, C. -Y.; Mathews, I. I. Proceedings of the National Academy of Sciences, Vol. 103, Issue 30 https://doi.org/10.1073/pnas.0601924103	journal	July 2006
Using Chemobiosynthesis and Synthetic Mini-Polyketide Synthases To Produce Pharmaceutical Intermediates in Escherichia coli Menzella, Hugo G.; Carney, John R.; Li, Yong Applied and Environmental Microbiology, Vol. 76, Issue 15 https://doi.org/10.1128/AEM.02961-09	journal	August 2010
Visualizing the Chain‐Flipping Mechanism in Fatty‐Acid Biosynthesis Beld, Joris; Cang, Hu; Burkart, Michael D. Angewandte Chemie, Vol. 126, Issue 52 https://doi.org/10.1002/ange.201408576	journal	October 2014
Preparative production of an enantiomeric pair by engineered polyketide synthases Miyazawa, Takeshi; Fitzgerald, Brendan J.; Keatinge-Clay, Adrian T. Chemical Communications, Vol. 57, Issue 70 https://doi.org/10.1039/D1CC03073F	journal	January 2021
Diversity oriented biosynthesis via accelerated evolution of modular gene clusters Wlodek, Aleksandra; Kendrew, Steve G.; Coates, Nigel J. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01344-3	journal	October 2017
Modification and de novo design of non-ribosomal peptide synthetases using specific assembly points within condensation domains Bozhüyük, Kenan A. J.; Linck, Annabell; Tietze, Andreas Nature Chemistry, Vol. 11, Issue 7 https://doi.org/10.1038/s41557-019-0276-z	journal	June 2019
Evolution of Efficient Modular Polyketide Synthases by Homologous Recombination Chemler, Joseph A.; Tripathi, Ashootosh; Hansen, Douglas A. Journal of the American Chemical Society, Vol. 137, Issue 33 https://doi.org/10.1021/jacs.5b04842	journal	August 2015
De novo protein design by deep network hallucination Anishchenko, Ivan; Pellock, Samuel J.; Chidyausiku, Tamuka M. Nature, Vol. 600, Issue 7889 https://doi.org/10.1038/s41586-021-04184-w	journal	December 2021
Enzymology of assembly line synthesis by modular polyketide synthases Grininger, Martin Nature Chemical Biology, Vol. 19, Issue 4 https://doi.org/10.1038/s41589-023-01277-7	journal	March 2023
The modules of trans -acyltransferase assembly lines redefined with a central acyl carrier protein Vander Wood, Drew A.; Keatinge-Clay, Adrian T. Proteins: Structure, Function, and Bioinformatics, Vol. 86, Issue 6 https://doi.org/10.1002/prot.25493	journal	March 2018
How cis-Acyltransferase Assembly-Line Ketosynthases Gatekeep for Processed Polyketide Intermediates Hirsch, Melissa; Fitzgerald, Brendan J.; Keatinge-Clay, Adrian T. ACS Chemical Biology, Vol. 16, Issue 11 https://doi.org/10.1021/acschembio.1c00598	journal	September 2021
Structural and Mechanistic Analysis of Protein Interactions in Module 3 of the 6-Deoxyerythronolide B Synthase Tang, Yinyan; Chen, Alice Y.; Kim, Chu-Young Chemistry & Biology, Vol. 14, Issue 8 https://doi.org/10.1016/j.chembiol.2007.07.012	journal	August 2007
Structural insights into dehydratase substrate selection for the borrelidin and fluvirucin polyketide synthases Barajas, Jesus F.; McAndrew, Ryan P.; Thompson, Mitchell G. Journal of Industrial Microbiology & Biotechnology, Vol. 46, Issue 8 https://doi.org/10.1007/s10295-019-02189-z	journal	May 2019
antiSMASH 6.0: improving cluster detection and comparison capabilities Blin, Kai; Shaw, Simon; Kloosterman, Alexander M. Nucleic Acids Research, Vol. 49, Issue W1 https://doi.org/10.1093/nar/gkab335	journal	May 2021
Divergence of multimodular polyketide synthases revealed by a didomain structure Zheng, Jianting; Gay, Darren C.; Demeler, Borries Nature Chemical Biology, Vol. 8, Issue 7 https://doi.org/10.1038/nchembio.964	journal	May 2012
Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida Anzai, Yojiro; Saito, Natsumi; Tanaka, Michiyasu FEMS Microbiology Letters, Vol. 218, Issue 1 https://doi.org/10.1111/j.1574-6968.2003.tb11509.x	journal	January 2003
Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection Nguyen, TuAnh; Ishida, Keishi; Jenke-Kodama, Holger Nature Biotechnology, Vol. 26, Issue 2 https://doi.org/10.1038/nbt1379	journal	January 2008
Molecular basis for interactions between an acyl carrier protein and a ketosynthase Milligan, Jacob C.; Lee, D. John; Jackson, David R. Nature Chemical Biology, Vol. 15, Issue 7 https://doi.org/10.1038/s41589-019-0301-y	journal	June 2019
Structure of a modular polyketide synthase Dutta, Somnath; Whicher, Jonathan R.; Hansen, Douglas A. Nature, Vol. 510, Issue 7506 https://doi.org/10.1038/nature13423	journal	June 2014
Protein-Protein Interactions, Not Substrate Recognition, Dominate the Turnover of Chimeric Assembly Line Polyketide Synthases Klaus, Maja; Ostrowski, Matthew P.; Austerjost, Jonas Journal of Biological Chemistry, Vol. 291, Issue 31 https://doi.org/10.1074/jbc.M116.730531	journal	May 2016
Modular polyketide synthase contains two reaction chambers that operate asynchronously Bagde, Saket R.; Mathews, Irimpan I.; Fromme, J. Christopher Science, Vol. 374, Issue 6568 https://doi.org/10.1126/science.abi8532	journal	November 2021
Solution Structure and Conformational Flexibility of a Polyketide Synthase Module Klaus, Maja; Rossini, Emanuele; Linden, Andreas JACS Au, Vol. 1, Issue 12 https://doi.org/10.1021/jacsau.1c00043	journal	October 2021
Priming enzymes from the pikromycin synthase reveal how assembly-line ketosynthases catalyze carbon-carbon chemistry Dickinson, Miles S.; Miyazawa, Takeshi; McCool, Ryan S. Structure, Vol. 30, Issue 9 https://doi.org/10.1016/j.str.2022.05.021	journal	September 2022
Structural Basis for Binding Specificity between Subclasses of Modular Polyketide Synthase Docking Domains Buchholz, Tonia J.; Geders, Todd W.; Bartley, Frank E. ACS Chemical Biology, Vol. 4, Issue 1 https://doi.org/10.1021/cb8002607	journal	January 2009
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: Versatility from a unique substrate channel Tsai, S. -C.; Miercke, L. J. W.; Krucinski, J. Proceedings of the National Academy of Sciences, Vol. 98, Issue 26 https://doi.org/10.1073/pnas.011399198	journal	December 2001
Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases Patel, Ketan D.; MacDonald, Monica R.; Ahmed, Syed Fardin Natural Product Reports, Vol. 40, Issue 9 https://doi.org/10.1039/D3NP00003F	journal	January 2023
ColabFold: making protein folding accessible to all Mirdita, Milot; Schütze, Konstantin; Moriwaki, Yoshitaka Nature Methods, Vol. 19, Issue 6 https://doi.org/10.1038/s41592-022-01488-1	journal	May 2022
Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase Kalkreuter, Edward; Bingham, Kyle S.; Keeler, Aaron M. Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-22497-2	journal	April 2021
Polyketide Synthase Modules Redefined Keatinge-Clay, Adrian T. Angewandte Chemie International Edition, Vol. 56, Issue 17 https://doi.org/10.1002/anie.201701281	journal	March 2017
Evolutionary-scale prediction of atomic-level protein structure with a language model Lin, Zeming; Akin, Halil; Rao, Roshan Science, Vol. 379, Issue 6637 https://doi.org/10.1126/science.ade2574	journal	March 2023
The Crystal Structure of a Mammalian Fatty Acid Synthase Maier, T.; Leibundgut, M.; Ban, N. Science, Vol. 321, Issue 5894 https://doi.org/10.1126/science.1161269	journal	September 2008
Discovery of Novel Gain-of-Function Mutations Guided by Structure-Based Deep Learning Shroff, Raghav; Cole, Austin W.; Diaz, Daniel J. ACS Synthetic Biology, Vol. 9, Issue 11 https://doi.org/10.1021/acssynbio.0c00345	journal	October 2020
DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking Corso, Gabriele; Stärk, Hannes; Jing, Bowen arXiv https://doi.org/10.48550/arXiv.2210.01776	preprint	January 2022
Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries Englund, Elias; Schmidt, Matthias; Nava, Alberto A. Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-40464-x	journal	August 2023
Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase Kapur, S.; Chen, A. Y.; Cane, D. E. Proceedings of the National Academy of Sciences, Vol. 107, Issue 51 https://doi.org/10.1073/pnas.1014081107	journal	December 2010
Machine learning-aided engineering of hydrolases for PET depolymerization Lu, Hongyuan; Diaz, Daniel J.; Czarnecki, Natalie J. Nature, Vol. 604, Issue 7907 https://doi.org/10.1038/s41586-022-04599-z	journal	April 2022
Crystal Structure of the Acyltransferase Domain of the Iterative Polyketide Synthase in Enediyne Biosynthesis Liew, Chong Wai; Nilsson, Martina; Chen, Ming Wei Journal of Biological Chemistry, Vol. 287, Issue 27 https://doi.org/10.1074/jbc.M112.362210	journal	May 2012
Biofuels for a sustainable future Liu, Yuzhong; Cruz-Morales, Pablo; Zargar, Amin Cell, Vol. 184, Issue 6 https://doi.org/10.1016/j.cell.2021.01.052	journal	March 2021
Stereocontrol within polyketide assembly lines Keatinge-Clay, Adrian T. Natural Product Reports, Vol. 33, Issue 2 https://doi.org/10.1039/C5NP00092K	journal	January 2016
Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes Menzella, Hugo G.; Reid, Ralph; Carney, John R. Nature Biotechnology, Vol. 23, Issue 9 https://doi.org/10.1038/nbt1128	journal	August 2005
An in vitro platform for engineering and harnessing modular polyketide synthases Miyazawa, Takeshi; Hirsch, Melissa; Zhang, Zhicheng Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-13811-0	journal	January 2020
Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides Zhang, Lihan; Hashimoto, Takuya; Qin, Bin Angewandte Chemie International Edition, Vol. 56, Issue 7 https://doi.org/10.1002/anie.201611371	journal	January 2017
Structure and Function of BorB, the Type II Thioesterase from the Borrelidin Biosynthetic Gene Cluster Curran, Samuel C.; Pereira, Jose H.; Baluyot, Marian-Joy Biochemistry, Vol. 59, Issue 16 https://doi.org/10.1021/acs.biochem.0c00126	journal	April 2020
Computed structures of core eukaryotic protein complexes Humphreys, Ian R.; Pei, Jimin; Baek, Minkyung Science, Vol. 374, Issue 6573 https://doi.org/10.1126/science.abm4805	journal	December 2021
Cyanobacterial Polyketide Synthase Docking Domains: A Tool for Engineering Natural Product Biosynthesis Whicher, Jonathan R.; Smaga, Sarah S.; Hansen, Douglas A. Chemistry & Biology, Vol. 20, Issue 11 https://doi.org/10.1016/j.chembiol.2013.09.015	journal	November 2013
Large language models generate functional protein sequences across diverse families Madani, Ali; Krause, Ben; Greene, Eric R. Nature Biotechnology, Vol. 41, Issue 8 https://doi.org/10.1038/s41587-022-01618-2	journal	January 2023
Engineered polyketides: Synergy between protein and host level engineering Barajas, Jesus F.; Blake-Hedges, Jacquelyn M.; Bailey, Constance B. Synthetic and Systems Biotechnology, Vol. 2, Issue 3 https://doi.org/10.1016/j.synbio.2017.08.005	journal	September 2017
Evaluating Ketoreductase Exchanges as a Means of Rationally Altering Polyketide Stereochemistry Annaval, Thibault; Paris, Cédric; Leadlay, Peter F. ChemBioChem, Vol. 16, Issue 9 https://doi.org/10.1002/cbic.201500113	journal	May 2015
Architectures of Whole-Module and Bimodular Proteins from the 6-Deoxyerythronolide B Synthase Edwards, Andrea L.; Matsui, Tsutomu; Weiss, Thomas M. Journal of Molecular Biology, Vol. 426, Issue 11 https://doi.org/10.1016/j.jmb.2014.03.015	journal	May 2014

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59 BASIC BIOLOGICAL SCIENCES
polyketide synthases
structural modeling
retrobiosynthesis
protein engineering

Title: Module-Based Polyketide Synthase Engineering for de Novo Polyketide Biosynthesis

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