Insights into Polyketide Biosynthesis Gained from Repurposing Antibiotic-producing Polyketide Synthases to Produce Fuels and Chemicals

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2016 Jun 2

PMID 27245558

Citations 8

Authors

Satoshi Yuzawa

Jay D Keasling

Leonard Katz

Affiliations

Soon will be listed here.

Abstract

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.

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