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

Autor: Cao F; Research Center for Clinical Pharmacy, The First Affiliated Hospital & Institute of Pharmaceutical Biotechnology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.; Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, Zhejiang University, Hangzhou, 310058, China., Ma LF; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China., Hu LS; Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China., Xu CX; Research Center for Clinical Pharmacy, The First Affiliated Hospital & Institute of Pharmaceutical Biotechnology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.; Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, Zhejiang University, Hangzhou, 310058, China., Chen X; Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China., Zhan ZJ; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China., Zhao QW; Research Center for Clinical Pharmacy, The First Affiliated Hospital & Institute of Pharmaceutical Biotechnology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.; Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, Zhejiang University, Hangzhou, 310058, China., Mao XM; Research Center for Clinical Pharmacy, The First Affiliated Hospital & Institute of Pharmaceutical Biotechnology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.; Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, Zhejiang University, Hangzhou, 310058, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Jan 26; Vol. 62 (5), pp. e202214814. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1002/anie.202214814
Abstrakt: 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.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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