Biosynthesis of 6‐Hydroxymellein Requires a Collaborating Polyketide Synthase‐like Enzyme

The polyketide synthase (PKS)‐like protein TerB, consisting of inactive dehydratase, inactive C‐methyltransferase, and functional ketoreductase domains collaborates with the iterative non reducing PKS TerA to produce 6‐hydroxymellein, a key pathway intermediate during the biosynthesis of various fun...

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Bibliographic Details
Published inAngewandte Chemie Vol. 133; no. 20; pp. 11524 - 11530
Main Authors Kahlert, Lukas, Villanueva, Miranda, Cox, Russell J., Skellam, Elizabeth J.
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 10.05.2021
Subjects
Biosynthesis
Chemistry
Dehydration
Domains
iterative polyketide synthase
ketoreductase
mellein
Methyltransferase
Natural products
Polyketide synthase
terrein
trans-acting domain
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Summary:The polyketide synthase (PKS)‐like protein TerB, consisting of inactive dehydratase, inactive C‐methyltransferase, and functional ketoreductase domains collaborates with the iterative non reducing PKS TerA to produce 6‐hydroxymellein, a key pathway intermediate during the biosynthesis of various fungal natural products. The catalytically inactive dehydratase domain of TerB appears to mediate productive interactions with TerA, demonstrating a new mode of trans‐interaction between iterative PKS components. A new architecture for iterative Type I polyketide synthases (PKS) from fungi has been investigated. TerA is a canonical non‐reducing PKS which interacts with TerB, a fragment of a highly reducing PKS containing a functional ketoreductase. Interaction appears to be mediated between a non‐functional dehydratase domain of TerB and the TerA product template domain. Working together, TerAB synthesises 6‐hydroxymellein, a precursor of terrein and other fungal metabolites.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202100969