Insights into polyketide biosynthesis gained from repurposing antibiotic-producing polyketide synthases to produce fuels and chemicals

Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from enzyme complexes named type I polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzyma...

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Published inJournal of antibiotics Vol. 69; no. 7; pp. 494 - 499
Main Authors Yuzawa, Satoshi, Keasling, Jay D, Katz, Leonard
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.07.2016
Nature Publishing Group
Japan Antibiotics Research Association - Springer
Subjects
38
60 APPLIED LIFE SCIENCES
631/61/252
631/92/60
631/92/95
Anti-Bacterial Agents - biosynthesis
Bacteriology
BASIC BIOLOGICAL SCIENCES
Biofuels
Biomedical and Life Sciences
Bioorganic Chemistry
Biosynthesis
Catalytic Domain
Fuels
Life Sciences
Medicinal Chemistry
Microbiology
Organic Chemistry
Polyketide Synthases - chemistry
Polyketide Synthases - genetics
Polyketide Synthases - metabolism
Polyketides - metabolism
Protein Engineering
review-article
Stereoisomerism
Substrate Specificity
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Summary:Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from enzyme complexes named type I polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides with enhanced or new properties. We have repurposed PKSs, employing up to three modules to produce a number of short-chain molecules that could have applications as fuels or industrial chemicals. Examining the enzymatic functions in vitro of these repurposed PKSs, we have uncovered a number of expanded substrate specificities and requirements of various PKS domains not previously reported and determined an unexpected difference in the order of enzymatic reactions within a module. In addition, we were able to efficiently change the stereochemistry of side chains in selected PKS products.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
AC02-05CH11231
USDOE Office of Science (SC), Biological and Environmental Research (BER)
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2016.64