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Title: 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:
ORCiD logo [1];  [2];  [3];  [4];  [2];  [5];  [5];  [2];  [2];  [2];  [6];  [7];  [6]; ORCiD logo [5];  [8]; ORCiD logo [9]
  1. 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
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division, and Advanced Biofuels & Bioproducts Process Development Unit
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division
  4. 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
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biogical Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States)
  6. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States)
  7. Sandia National Lab. (SNL-CA), Livermore, CA (United States)
  8. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). QB3 Inst.
  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 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:
Journal Article: 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. 2018. "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},
url = {https://www.osti.gov/biblio/1493265}, journal = {Nature Communications},
issn = {2041-1723},
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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Cited by: 33 works
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Figures / Tables:

Figure 1 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 » (blue) is derived from the erythromycin PKS. The AT domain shown in magenta is derived from the borrelidin PKS module 1, which is specific for malonyl-CoA. Enzymatic products that can be produced by each PKS were shown in the same box. AT acyltransferase, ACP acyl carrier protein, CoA coenzyme A, KAL KS to AT linker, KR ketoreductase, KS ketosynthetas, PAL Post AT linker, TE thioesterase« less

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Works referenced in this record:

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Metabolic engineering of 2-pentanone synthesis in Escherichia coli
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Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters
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Substantial improvements in methyl ketone production in E. coli and insights on the pathway from in vitro studies
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Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production
journal, July 2015


Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro
journal, June 2018


Development of Next Generation Synthetic Biology Tools for Use in Streptomyces venezuelae
journal, September 2016


Broad Substrate Specificity of the Loading Didomain of the Lipomycin Polyketide Synthase
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Enzyme analysis of the polyketide synthase leads to the discovery of a novel analog of the antibiotic α-lipomycin
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Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals
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Microbial production of short-chain alkanes
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Microbial synthesis of medium-chain chemicals from renewables
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Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway
journal, November 2015


Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces
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An Engineered Strong Promoter for Streptomycetes
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Selection Criteria and Screening of Potential Biomass-Derived Streams as Fuel Blendstocks for Advanced Spark-Ignition Engines
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Works referencing / citing this record:

Construction of a new integrating vector from actinophage ϕOZJ and its use in multiplex Streptomyces transformation
journal, November 2019


Technical Advances to Accelerate Modular Type I Polyketide Synthase Engineering towards a Retro-biosynthetic Platform
journal, June 2019


Highlights of Streptomyces genetics
journal, June 2019


Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids
journal, January 2020


Modular and Integrative Vectors for Synthetic Biology Applications in Streptomyces spp.
journal, June 2019


Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.