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A fungal ketoreductase domain that displays substrate-dependent stereospecificity.


ABSTRACT: Iterative highly reducing polyketide synthases from filamentous fungi are the most complex and enigmatic type of polyketide synthase discovered to date. Here we uncover an unusual degree of programming by the hypothemycin highly reducing polyketide synthase, in which a single ketoreductase domain shows stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed for the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.

SUBMITTER: Zhou H 

PROVIDER: S-EPMC3307869 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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A fungal ketoreductase domain that displays substrate-dependent stereospecificity.

Zhou Hui H   Gao Zhizeng Z   Qiao Kangjian K   Wang Jingjing J   Vederas John C JC   Tang Yi Y  

Nature chemical biology 20120311 4


Iterative highly reducing polyketide synthases from filamentous fungi are the most complex and enigmatic type of polyketide synthase discovered to date. Here we uncover an unusual degree of programming by the hypothemycin highly reducing polyketide synthase, in which a single ketoreductase domain shows stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed for the biosynthesis of an unnatural diastereomer of the natural pr  ...[more]

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