Short-chain ketone production by engineered polyketide synthases in Streptomyces albus

Yuzawa, Satoshi; Mirsiaghi, Mona; Jocic, Renee; Fujii, Tatsuya; Masson, Fabrice; Benites, Veronica T.; Baidoo, Edward E.  K.; Sundstrom, Eric; Tanjore, Deepti; Pray, Todd R.; George, Anthe; Davis, Ryan W.; Gladden, John M.; Simmons, Blake A.; Katz, Leonard; Keasling, Jay D.

doi:10.1038/s41467-018-07040-0

Title: Short-chain ketone production by engineered polyketide synthases in Streptomyces albus

Journal Article · Thu Nov 01 00:00:00 EDT 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-07040-0· OSTI ID:1493265

^[1]; Mirsiaghi, Mona ^[2]; Jocic, Renee ^[3]; Fujii, Tatsuya ^[4]; Masson, Fabrice ^[2]; Benites, Veronica T. ^[5]; Baidoo, Edward E. K. ^[5]; Sundstrom, Eric ^[2]; Tanjore, Deepti ^[2]; Pray, Todd R. ^[2]; George, Anthe ^[6]; Davis, Ryan W. ^[7]; Gladden, John M. ^[6];

^[5]; Katz, Leonard ^[8];

^[9]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of Tokyo (Japan). Biotechnology Research Center
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division, and Advanced Biofuels & Bioproducts Process Development Unit
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); National Inst. of Advanced Industrial Science and Technology, Higashi-hiroshima, Hiroshima (Japan). Research Inst. for Sustainable Chemistry, Inst. for Synthetic Biology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States)
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). QB3 Inst.
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). QB3 Inst., Dept. of Bioengineering, Dept. of Chemical and Biomolecular Engineering; Technical Univ. of Denmark, Lyngby (Denmark). Novo Nordisk Foundation Center for Biosustainability; Shenzhen Inst. for Advanced Technologies, Shenzhen, Guangdong (China). Center for Synthetic Biochemistry

Microbial production of fuels and commodity chemicals has been performed primarily using natural or slightly modified enzymes, which inherently limits the types of molecules that can be produced. Type I modular polyketide synthases (PKSs) are multi-domain enzymes that can produce unique and diverse molecular structures by combining particular types of catalytic domains in a specific order. This catalytic mechanism offers a wealth of engineering opportunities. Here we report engineered microbes that produce various short-chain (C5-C7) ketones using hybrid PKSs. Introduction of the genes into the chromosome of Streptomyces albus enables it to produce >1 g · l^-1 of C6 and C7 ethyl ketones and several hundred mg · l^-1 of C5 and C6 methyl ketones from plant biomass hydrolysates. Engine tests indicate these short-chain ketones can be added to gasoline as oxygenates to increase the octane of gasoline. Together, it demonstrates the efficient and renewable microbial production of biogasolines by hybrid enzymes.

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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); National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1493265

Journal Information:: Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 33 works

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References (32)

Minimum Information about a Biosynthetic Gene cluster Medema, Marnix H.; Kottmann, Renzo; Yilmaz, Pelin Nature Chemical Biology, Vol. 11, Issue 9 https://doi.org/10.1038/nchembio.1890	journal	August 2015
Heterologous Gene Expression of N -Terminally Truncated Variants of LipPks1 Suggests a Functionally Critical Structural Motif in the N -terminus of Modular Polyketide Synthase Yuzawa, Satoshi; Bailey, Constance B.; Fujii, Tatsuya ACS Chemical Biology, Vol. 12, Issue 11 https://doi.org/10.1021/acschembio.7b00714	journal	October 2017
Biosynthetic Gene Cluster for the Polyenoyltetramic Acid -Lipomycin Bihlmaier, C.; Welle, E.; Hofmann, C. Antimicrobial Agents and Chemotherapy, Vol. 50, Issue 6 https://doi.org/10.1128/AAC.00007-06	journal	May 2006
Engineering Escherichia coli for Microbial Production of Butanone Srirangan, Kajan; Liu, Xuejia; Akawi, Lamees Applied and Environmental Microbiology, Vol. 82, Issue 9 https://doi.org/10.1128/AEM.03964-15	journal	February 2016
Engineering of Ralstonia eutropha H16 for Autotrophic and Heterotrophic Production of Methyl Ketones Muller, J.; MacEachran, D.; Burd, H. Applied and Environmental Microbiology, Vol. 79, Issue 14 https://doi.org/10.1128/AEM.00973-13	journal	May 2013
Engineering high-level production of fatty alcohols by Saccharomyces cerevisiae from lignocellulosic feedstocks d’Espaux, Leo; Ghosh, Amit; Runguphan, Weerawat Metabolic Engineering, Vol. 42 https://doi.org/10.1016/j.ymben.2017.06.004	journal	July 2017
Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals Dellomonaco, Clementina; Clomburg, James M.; Miller, Elliot N. Nature, Vol. 476, Issue 7360, p. 355-359 https://doi.org/10.1038/nature10333	journal	August 2011
Microbial production of short-chain alkanes Choi, Yong Jun; Lee, Sang Yup Nature, Vol. 502, Issue 7472 https://doi.org/10.1038/nature12536	journal	September 2013
Enzyme analysis of the polyketide synthase leads to the discovery of a novel analog of the antibiotic α-lipomycin Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard The Journal of Antibiotics, Vol. 67, Issue 2 https://doi.org/10.1038/ja.2013.110	journal	October 2013
Microbial synthesis of medium-chain chemicals from renewables Sarria, Stephen; Kruyer, Nicholas S.; Peralta-Yahya, Pamela Nature Biotechnology, Vol. 35, Issue 12 https://doi.org/10.1038/nbt.4022	journal	December 2017
Expanding the product portfolio of fungal type I fatty acid synthases Zhu, Zhiwei; Zhou, Yongjin J.; Krivoruchko, Anastasia Nature Chemical Biology, Vol. 13, Issue 4 https://doi.org/10.1038/nchembio.2301	journal	February 2017
Development of Next Generation Synthetic Biology Tools for Use in Streptomyces venezuelae Phelan, Ryan M.; Sachs, Daniel; Petkiewicz, Shayne J. ACS Synthetic Biology, Vol. 6, Issue 1 https://doi.org/10.1021/acssynbio.6b00202	journal	September 2016
Substantial improvements in methyl ketone production in E. coli and insights on the pathway from in vitro studies Goh, Ee-Been; Baidoo, Edward E. K.; Burd, Helcio Metabolic Engineering, Vol. 26 https://doi.org/10.1016/j.ymben.2014.09.003	journal	November 2014
Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters Baltz, Richard H. Journal of Industrial Microbiology & Biotechnology, Vol. 37, Issue 8 https://doi.org/10.1007/s10295-010-0730-9	journal	May 2010
Engineering a synthetic pathway in cyanobacteria for isopropanol production directly from carbon dioxide and light Kusakabe, Tamami; Tatsuke, Tsuneyuki; Tsuruno, Keigo Metabolic Engineering, Vol. 20 https://doi.org/10.1016/j.ymben.2013.09.007	journal	November 2013
Selection Criteria and Screening of Potential Biomass-Derived Streams as Fuel Blendstocks for Advanced Spark-Ignition Engines McCormick, Robert L.; Fioroni, Gina; Fouts, Lisa SAE International Journal of Fuels and Lubricants, Vol. 10, Issue 2 https://doi.org/10.4271/2017-01-0868	journal	March 2017
Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces Bai, Chaoxian; Zhang, Yang; Zhao, Xuejin Proceedings of the National Academy of Sciences, Vol. 112, Issue 39 https://doi.org/10.1073/pnas.1511027112	journal	September 2015
Broad Substrate Specificity of the Loading Didomain of the Lipomycin Polyketide Synthase Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard Biochemistry, Vol. 52, Issue 22 https://doi.org/10.1021/bi400520t	journal	May 2013
Prodigal: prokaryotic gene recognition and translation initiation site identification Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F. BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-119	journal	March 2010
Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production Haushalter, Robert W.; Groff, Dan; Deutsch, Samuel Metabolic Engineering, Vol. 30 https://doi.org/10.1016/j.ymben.2015.04.003	journal	July 2015
Microbial Biosynthesis of Alkanes Schirmer, A.; Rude, M. A.; Li, X. Science, Vol. 329, Issue 5991, p. 559-562 https://doi.org/10.1126/science.1187936	journal	July 2010
Engineering 1-Alkene Biosynthesis and Secretion by Dynamic Regulation in Yeast Zhou, Yongjin J.; Hu, Yating; Zhu, Zhiwei ACS Synthetic Biology, Vol. 7, Issue 2 https://doi.org/10.1021/acssynbio.7b00338	journal	January 2018
Comprehensive in Vitro Analysis of Acyltransferase Domain Exchanges in Modular Polyketide Synthases and Its Application for Short-Chain Ketone Production Yuzawa, Satoshi; Deng, Kai; Wang, George ACS Synthetic Biology, Vol. 6, Issue 1 https://doi.org/10.1021/acssynbio.6b00176	journal	September 2016
Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway Mak, Wai Shun; Tran, Stephen; Marcheschi, Ryan Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms10005	journal	November 2015
Metabolic engineering of 2-pentanone synthesis in Escherichia coli Lan, Ethan I.; Dekishima, Yasumasa; Chuang, Derrick S. AIChE Journal, Vol. 59, Issue 9 https://doi.org/10.1002/aic.14086	journal	April 2013
The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site Bibb, Mervyn J.; White, Janet; Ward, Judith M. Molecular Microbiology, Vol. 14, Issue 3 https://doi.org/10.1111/j.1365-2958.1994.tb02187.x	journal	November 1994
High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineeredEscherichia coli Newman, Jack D.; Marshall, Jessica; Chang, Michelle Biotechnology and Bioengineering, Vol. 95, Issue 4 https://doi.org/10.1002/bit.21017	journal	January 2006
Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro Curran, Samuel C.; Hagen, Andrew; Poust, Sean ACS Chemical Biology, Vol. 13, Issue 8 https://doi.org/10.1021/acschembio.8b00422	journal	June 2018
Medium optimization of Streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J Rateb, Mostafa E.; Yu, Zhiguo; Yan, Yijun The Journal of Antibiotics, Vol. 67, Issue 1 https://doi.org/10.1038/ja.2013.50	journal	May 2013
Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids Bowen, Christopher H.; Bonin, Jeff; Kogler, Anna ACS Synthetic Biology, Vol. 5, Issue 3 https://doi.org/10.1021/acssynbio.5b00201	journal	December 2015
Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels Atsumi, Shota; Hanai, Taizo; Liao, James C. Nature, Vol. 451, Issue 7174, p. 86-89 https://doi.org/10.1038/nature06450	journal	January 2008
An Engineered Strong Promoter for Streptomycetes Wang, W.; Li, X.; Wang, J. Applied and Environmental Microbiology, Vol. 79, Issue 14 https://doi.org/10.1128/aem.00985-13	journal	May 2013

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Technical Advances to Accelerate Modular Type I Polyketide Synthase Engineering towards a Retro-biosynthetic Platform Pang, Bo; Valencia, Luis E.; Wang, Jessica Biotechnology and Bioprocess Engineering, Vol. 24, Issue 3 https://doi.org/10.1007/s12257-019-0083-9	journal	June 2019
Highlights of Streptomyces genetics Hopwood, David A. Heredity, Vol. 123, Issue 1 https://doi.org/10.1038/s41437-019-0196-0	journal	June 2019
Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids Zhu, Zhiwei; Hu, Yating; Teixeira, Paulo Gonçalves Nature Catalysis, Vol. 3, Issue 1 https://doi.org/10.1038/s41929-019-0409-1	journal	January 2020
Modular and Integrative Vectors for Synthetic Biology Applications in Streptomyces spp. Aubry, Céline; Pernodet, Jean-Luc; Lautru, Sylvie Applied and Environmental Microbiology, Vol. 85, Issue 16 https://doi.org/10.1128/aem.00485-19	journal	June 2019

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