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Cross‐Module Enoylreduction in the Azalomycin F Polyketide Synthase
Author(s) -
Zhai Guifa,
Wang Wenyan,
Xu Wei,
Sun Guo,
Hu Chaoqun,
Wu Xiangming,
Cong Zisong,
Deng Liang,
Shi Yanrong,
Leadlay Peter F.,
Song Heng,
Hong Kui,
Deng Zixin,
Sun Yuhui
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202011357
Subject(s) - polyketide synthase , polyketide , modular design , computational biology , biosynthesis , stereochemistry , atp synthase , reductase , biology , enzyme , chemistry , biochemistry , computer science , programming language
The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end‐product, has become a cornerstone of knowledge‐based genome mining. Herein, we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown to also catalyze enoylreduction in trans within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross‐modular interaction of the reductase with the longer acyl chain, rather than back transfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly‐line catalysis.