Short-chain ketone production by engineered polyketide synthases in Streptomyces albus
Abstract
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.
- Authors:
-
[1];
[5];
[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
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)
- OSTI Identifier:
- 1493265
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
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, and Keasling, Jay D. Short-chain ketone production by engineered polyketide synthases in Streptomyces albus. United States: N. p., 2018.
Web. doi:10.1038/s41467-018-07040-0.
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. Short-chain ketone production by engineered polyketide synthases in Streptomyces albus. United States. https://doi.org/10.1038/s41467-018-07040-0
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, and Keasling, Jay D. Thu .
"Short-chain ketone production by engineered polyketide synthases in Streptomyces albus". United States. https://doi.org/10.1038/s41467-018-07040-0. https://www.osti.gov/servlets/purl/1493265.
@article{osti_1493265,
title = {Short-chain ketone production by engineered polyketide synthases in Streptomyces albus},
author = {Yuzawa, Satoshi and Mirsiaghi, Mona and Jocic, Renee and Fujii, Tatsuya and Masson, Fabrice and Benites, Veronica T. and Baidoo, Edward E. K. and Sundstrom, Eric and Tanjore, Deepti and Pray, Todd R. and George, Anthe and Davis, Ryan W. and Gladden, John M. and Simmons, Blake A. and Katz, Leonard and Keasling, Jay D.},
abstractNote = {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.},
doi = {10.1038/s41467-018-07040-0},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {Thu Nov 01 00:00:00 EDT 2018},
month = {Thu Nov 01 00:00:00 EDT 2018}
}
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Figures / Tables:
Figure 1: Hybrid polyketide synthases engineered to produce short-chain ketones. Short-chain ketone-producing polyketide synthases (PKSs) were created by engineering of LipPks1, a type I modular PKS. Catalytic domains of LipPks1 are shown in green. The non-catalytic domains are shown in gray. Linkers are shown as black line. The TE domainmore »
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Works referenced in this record:
Minimum Information about a Biosynthetic Gene cluster
journal, August 2015
- Medema, Marnix H.; Kottmann, Renzo; Yilmaz, Pelin
- Nature Chemical Biology, Vol. 11, Issue 9
Heterologous Gene Expression of N -Terminally Truncated Variants of LipPks1 Suggests a Functionally Critical Structural Motif in the N -terminus of Modular Polyketide Synthase
journal, October 2017
- Yuzawa, Satoshi; Bailey, Constance B.; Fujii, Tatsuya
- ACS Chemical Biology, Vol. 12, Issue 11
Biosynthetic Gene Cluster for the Polyenoyltetramic Acid -Lipomycin
journal, May 2006
- Bihlmaier, C.; Welle, E.; Hofmann, C.
- Antimicrobial Agents and Chemotherapy, Vol. 50, Issue 6
Engineering Escherichia coli for Microbial Production of Butanone
journal, February 2016
- Srirangan, Kajan; Liu, Xuejia; Akawi, Lamees
- Applied and Environmental Microbiology, Vol. 82, Issue 9
Engineering of Ralstonia eutropha H16 for Autotrophic and Heterotrophic Production of Methyl Ketones
journal, May 2013
- Muller, J.; MacEachran, D.; Burd, H.
- Applied and Environmental Microbiology, Vol. 79, Issue 14
Engineering high-level production of fatty alcohols by Saccharomyces cerevisiae from lignocellulosic feedstocks
journal, July 2017
- d’Espaux, Leo; Ghosh, Amit; Runguphan, Weerawat
- Metabolic Engineering, Vol. 42
Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals
journal, August 2011
- Dellomonaco, Clementina; Clomburg, James M.; Miller, Elliot N.
- Nature, Vol. 476, Issue 7360, p. 355-359
Microbial production of short-chain alkanes
journal, September 2013
- Choi, Yong Jun; Lee, Sang Yup
- Nature, Vol. 502, Issue 7472
Enzyme analysis of the polyketide synthase leads to the discovery of a novel analog of the antibiotic α-lipomycin
journal, October 2013
- Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard
- The Journal of Antibiotics, Vol. 67, Issue 2
Microbial synthesis of medium-chain chemicals from renewables
journal, December 2017
- Sarria, Stephen; Kruyer, Nicholas S.; Peralta-Yahya, Pamela
- Nature Biotechnology, Vol. 35, Issue 12
Expanding the product portfolio of fungal type I fatty acid synthases
journal, February 2017
- Zhu, Zhiwei; Zhou, Yongjin J.; Krivoruchko, Anastasia
- Nature Chemical Biology, Vol. 13, Issue 4
Development of Next Generation Synthetic Biology Tools for Use in Streptomyces venezuelae
journal, September 2016
- Phelan, Ryan M.; Sachs, Daniel; Petkiewicz, Shayne J.
- ACS Synthetic Biology, Vol. 6, Issue 1
Substantial improvements in methyl ketone production in E. coli and insights on the pathway from in vitro studies
journal, November 2014
- Goh, Ee-Been; Baidoo, Edward E. K.; Burd, Helcio
- Metabolic Engineering, Vol. 26
Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters
journal, May 2010
- Baltz, Richard H.
- Journal of Industrial Microbiology & Biotechnology, Vol. 37, Issue 8
Engineering a synthetic pathway in cyanobacteria for isopropanol production directly from carbon dioxide and light
journal, November 2013
- Kusakabe, Tamami; Tatsuke, Tsuneyuki; Tsuruno, Keigo
- Metabolic Engineering, Vol. 20
Selection Criteria and Screening of Potential Biomass-Derived Streams as Fuel Blendstocks for Advanced Spark-Ignition Engines
journal, March 2017
- McCormick, Robert L.; Fioroni, Gina; Fouts, Lisa
- SAE International Journal of Fuels and Lubricants, Vol. 10, Issue 2
Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces
journal, September 2015
- Bai, Chaoxian; Zhang, Yang; Zhao, Xuejin
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 39
Broad Substrate Specificity of the Loading Didomain of the Lipomycin Polyketide Synthase
journal, May 2013
- Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard
- Biochemistry, Vol. 52, Issue 22
Prodigal: prokaryotic gene recognition and translation initiation site identification
journal, March 2010
- Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F.
- BMC Bioinformatics, Vol. 11, Issue 1
Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production
journal, July 2015
- Haushalter, Robert W.; Groff, Dan; Deutsch, Samuel
- Metabolic Engineering, Vol. 30
Microbial Biosynthesis of Alkanes
journal, July 2010
- Schirmer, A.; Rude, M. A.; Li, X.
- Science, Vol. 329, Issue 5991, p. 559-562
Engineering 1-Alkene Biosynthesis and Secretion by Dynamic Regulation in Yeast
journal, January 2018
- Zhou, Yongjin J.; Hu, Yating; Zhu, Zhiwei
- ACS Synthetic Biology, Vol. 7, Issue 2
Comprehensive in Vitro Analysis of Acyltransferase Domain Exchanges in Modular Polyketide Synthases and Its Application for Short-Chain Ketone Production
journal, September 2016
- Yuzawa, Satoshi; Deng, Kai; Wang, George
- ACS Synthetic Biology, Vol. 6, Issue 1
Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway
journal, November 2015
- Mak, Wai Shun; Tran, Stephen; Marcheschi, Ryan
- Nature Communications, Vol. 6, Issue 1
Metabolic engineering of 2-pentanone synthesis in Escherichia coli
journal, April 2013
- Lan, Ethan I.; Dekishima, Yasumasa; Chuang, Derrick S.
- AIChE Journal, Vol. 59, Issue 9
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
journal, November 1994
- Bibb, Mervyn J.; White, Janet; Ward, Judith M.
- Molecular Microbiology, Vol. 14, Issue 3
High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineeredEscherichia coli
journal, January 2006
- Newman, Jack D.; Marshall, Jessica; Chang, Michelle
- Biotechnology and Bioengineering, Vol. 95, Issue 4
Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro
journal, June 2018
- Curran, Samuel C.; Hagen, Andrew; Poust, Sean
- ACS Chemical Biology, Vol. 13, Issue 8
Medium optimization of Streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J
journal, May 2013
- Rateb, Mostafa E.; Yu, Zhiguo; Yan, Yijun
- The Journal of Antibiotics, Vol. 67, Issue 1
Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids
journal, December 2015
- Bowen, Christopher H.; Bonin, Jeff; Kogler, Anna
- ACS Synthetic Biology, Vol. 5, Issue 3
Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels
journal, January 2008
- Atsumi, Shota; Hanai, Taizo; Liao, James C.
- Nature, Vol. 451, Issue 7174, p. 86-89
Metabolic engineering of 2-pentanone synthesis in Escherichia coli
journal, April 2013
- Lan, Ethan I.; Dekishima, Yasumasa; Chuang, Derrick S.
- AIChE Journal, Vol. 59, Issue 9
High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineeredEscherichia coli
journal, January 2006
- Newman, Jack D.; Marshall, Jessica; Chang, Michelle
- Biotechnology and Bioengineering, Vol. 95, Issue 4
Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters
journal, May 2010
- Baltz, Richard H.
- Journal of Industrial Microbiology & Biotechnology, Vol. 37, Issue 8
Substantial improvements in methyl ketone production in E. coli and insights on the pathway from in vitro studies
journal, November 2014
- Goh, Ee-Been; Baidoo, Edward E. K.; Burd, Helcio
- Metabolic Engineering, Vol. 26
Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production
journal, July 2015
- Haushalter, Robert W.; Groff, Dan; Deutsch, Samuel
- Metabolic Engineering, Vol. 30
Heterologous Gene Expression of N -Terminally Truncated Variants of LipPks1 Suggests a Functionally Critical Structural Motif in the N -terminus of Modular Polyketide Synthase
journal, October 2017
- Yuzawa, Satoshi; Bailey, Constance B.; Fujii, Tatsuya
- ACS Chemical Biology, Vol. 12, Issue 11
Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro
journal, June 2018
- Curran, Samuel C.; Hagen, Andrew; Poust, Sean
- ACS Chemical Biology, Vol. 13, Issue 8
Development of Next Generation Synthetic Biology Tools for Use in Streptomyces venezuelae
journal, September 2016
- Phelan, Ryan M.; Sachs, Daniel; Petkiewicz, Shayne J.
- ACS Synthetic Biology, Vol. 6, Issue 1
Broad Substrate Specificity of the Loading Didomain of the Lipomycin Polyketide Synthase
journal, May 2013
- Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard
- Biochemistry, Vol. 52, Issue 22
Enzyme analysis of the polyketide synthase leads to the discovery of a novel analog of the antibiotic α-lipomycin
journal, October 2013
- Yuzawa, Satoshi; Eng, Clara H.; Katz, Leonard
- The Journal of Antibiotics, Vol. 67, Issue 2
Medium optimization of Streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J
journal, May 2013
- Rateb, Mostafa E.; Yu, Zhiguo; Yan, Yijun
- The Journal of Antibiotics, Vol. 67, Issue 1
Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals
journal, August 2011
- Dellomonaco, Clementina; Clomburg, James M.; Miller, Elliot N.
- Nature, Vol. 476, Issue 7360, p. 355-359
Microbial production of short-chain alkanes
journal, September 2013
- Choi, Yong Jun; Lee, Sang Yup
- Nature, Vol. 502, Issue 7472
Microbial synthesis of medium-chain chemicals from renewables
journal, December 2017
- Sarria, Stephen; Kruyer, Nicholas S.; Peralta-Yahya, Pamela
- Nature Biotechnology, Vol. 35, Issue 12
Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway
journal, November 2015
- Mak, Wai Shun; Tran, Stephen; Marcheschi, Ryan
- Nature Communications, Vol. 6, Issue 1
Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces
journal, September 2015
- Bai, Chaoxian; Zhang, Yang; Zhao, Xuejin
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 39
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
journal, November 1994
- Bibb, Mervyn J.; White, Janet; Ward, Judith M.
- Molecular Microbiology, Vol. 14, Issue 3
An Engineered Strong Promoter for Streptomycetes
journal, May 2013
- Wang, W.; Li, X.; Wang, J.
- Applied and Environmental Microbiology, Vol. 79, Issue 14
Prodigal: prokaryotic gene recognition and translation initiation site identification
journal, March 2010
- Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F.
- BMC Bioinformatics, Vol. 11, Issue 1
Selection Criteria and Screening of Potential Biomass-Derived Streams as Fuel Blendstocks for Advanced Spark-Ignition Engines
journal, March 2017
- McCormick, Robert L.; Fioroni, Gina; Fouts, Lisa
- SAE International Journal of Fuels and Lubricants, Vol. 10, Issue 2
Works referencing / citing this record:
Construction of a new integrating vector from actinophage ϕOZJ and its use in multiplex Streptomyces transformation
journal, November 2019
- Ko, Bryan; D’Alessandro, John; Douangkeomany, Lee
- Journal of Industrial Microbiology & Biotechnology, Vol. 47, Issue 1
Technical Advances to Accelerate Modular Type I Polyketide Synthase Engineering towards a Retro-biosynthetic Platform
journal, June 2019
- Pang, Bo; Valencia, Luis E.; Wang, Jessica
- Biotechnology and Bioprocess Engineering, Vol. 24, Issue 3
Highlights of Streptomyces genetics
journal, June 2019
- Hopwood, David A.
- Heredity, Vol. 123, Issue 1
Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids
journal, January 2020
- Zhu, Zhiwei; Hu, Yating; Teixeira, Paulo Gonçalves
- Nature Catalysis, Vol. 3, Issue 1
Modular and Integrative Vectors for Synthetic Biology Applications in Streptomyces spp.
journal, June 2019
- Aubry, Céline; Pernodet, Jean-Luc; Lautru, Sylvie
- Applied and Environmental Microbiology, Vol. 85, Issue 16
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