Ketoreductase Domain-Catalyzed Polyketide Chain Release in Fungal Alkyl Salicylaldehyde Biosynthesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Run Yang
  • Jian Feng
  • Hao Xiang
  • Bin Cheng
  • Li-Dong Shao
  • Yan-Ping Li
  • Hang Wang
  • Qiu-Fen Hu
  • Wei-Lie Xiao
  • Wei-Guang Wang

Detail(s)

Original languageEnglish
Pages (from-to)11293–11300
Journal / PublicationJournal of the American Chemical Society
Volume145
Issue number20
Online published12 May 2023
Publication statusPublished - 24 May 2023

Abstract

Alkyl salicylaldehyde derivatives are polyketide natural products, which are widely distributed in fungi and exhibit great structural diversity. Their biosynthetic mechanisms have recently been intensively studied; however, how the polyketide synthases (PKSs) involved in the fungal alkyl salicylaldehyde biosyntheses release their products remained elusive. In this study, we discovered an orphan biosynthetic gene cluster of salicylaldehyde derivatives in the fungus Stachybotrys sp. g12. Intriguingly, the highly reducing PKS StrA, encoded by the gene cluster, performs a reductive polyketide chain release, although it lacks a C-terminal reductase domain, which is typically required for such a reductive release. Our study revealed that the chain release is achieved by the ketoreductase (KR) domain of StrA, which also conducts cannonical β-keto reductions during polyketide chain elongation. Furthermore, we found that the cupin domain-containing protein StrC plays a critical role in the aromatization reaction. Collectively, we have provided an unprecedented example of a KR domain-catalyzed polyketide chain release and a clearer image of how the salicylaldehyde scaffold is generated in fungi. © 2023 American Chemical Society.

Citation Format(s)

Ketoreductase Domain-Catalyzed Polyketide Chain Release in Fungal Alkyl Salicylaldehyde Biosynthesis. / Yang, Run; Feng, Jian; Xiang, Hao et al.

In: Journal of the American Chemical Society, Vol. 145, No. 20, 24.05.2023, p. 11293–11300.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review