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Biological Chemistry

Polyketide Enzyme Module Makes Ring

Researchers find polyketide synthase module that generates ring in the linear backbone of polyketide natural products

by Stu Borman
September 23, 2013 | A version of this story appeared in Volume 91, Issue 38

An enzyme module that generates an unusual type of polyketide natural product has been found. The discovery could help further diversify combinatorial biosynthesis to create novel natural-product-like molecules for drug discovery and other applications. Polyketide synthases are enzyme systems that take simple precursor molecules and string them together to form polymeric products, such as the fungus-produced antimitotic and antitumor agent rhizoxin. Although polyketide synthase-produced molecular backbones often fold over to produce macrocyclic final products, polyketide synthase modules generally create linear backbones. Now, a module that fuses a ring onto an extending linear chain has been uncovered. The work was carried out by Georg Zocher of Eberhard Karls University, in Tübingen, Germany; Christian Hertweck of Leibniz Institute for Natural Product Research & Infection Biology, in Jena, Germany; and coworkers (Nature 2013, DOI: 10.1038/nature12588). “This behavior imparts a second dimension to biosynthesis catalyzed by these giant enzymes and potentially provides synthetic biologists with a tool to modify and rigidify polyketide synthase products in a predictable manner,” notes Craig A. Townsend of Johns Hopkins University in a Nature commentary.


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