Coordination of Polyketide Release and Multiple Detoxification Pathways for Tolerable Production of Fungal Mycotoxins

Autor: Fei Cao, Lie‐Feng Ma, Long‐Shuang Hu, Chu‐Xuan Xu, Xuepeng Chen, Zha‐Jun Zhan, Qing‐Wei Zhao, Xu‐Ming Mao
Rok vydání: 2022
Předmět:
Zdroj: Angewandte Chemie International Edition. 62
ISSN: 1521-3773
1433-7851
DOI: 10.1002/anie.202214814
Popis: Efficient biosynthesis of microbial bioactive natural products (NPs) is beneficial for the survival of producers, while self-protection is necessary to avoid self-harm resulting from over-accumulation of NPs. The underlying mechanisms for the effective but tolerable production of bioactive NPs are not well understood. Herein, in the biosynthesis of two fungal polyketide mycotoxins aurovertin E (1) and asteltoxin, we show that the cyclases in the gene clusters promote the release of the polyketide backbone, and reveal that a signal peptide is crucial for their subcellular localization and full activity. Meanwhile, the fungus adopts enzymatic acetylation as the major detoxification pathway of 1. If intermediates are over-produced, the non-enzymatic shunt pathways work as salvage pathways to avoid excessive accumulation of the toxic metabolites for self-protection. These findings provided new insight into the interplay of efficient backbone release and multiple detoxification strategies for the production of fungal bioactive NPs.
Databáze: OpenAIRE
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