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Identification and Characterization of the Chaetoviridin and Chaetomugilin Gene Cluster in Chaetomium globosum Reveal Dual Functions of an Iterative Highly-Reducing Polyketide Synthase

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Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, United States
Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
§ Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States
Cite this: J. Am. Chem. Soc. 2012, 134, 43, 17900–17903
Publication Date (Web):October 16, 2012
Copyright © 2012 American Chemical Society

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    We report the identification and characterization of the caz biosynthetic cluster from Chaetomium globosum and the characterization of a highly reducing polyketide synthase (PKS) that acts in both a sequential and convergent manner with a nonreducing PKS to form the chaetomugilin and chaetoviridin azaphilones. Genetic inactivation studies verified the involvement of individual caz genes in the biosynthesis of the azaphilones. Through in vitro reconstitution, we demonstrated the in vitro synthesis of chaetoviridin A from the pyranoquinone intermediate cazisochromene using the highly reducing PKS and an acyltransferase.

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