Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

Qiaolin Ji; Xingxing Wei; Shengkun Liu; Yudai Matsuda

doi:10.1021/acs.orglett.4c03675

Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

Qiaolin Ji, Xingxing Wei, Shengkun Liu, Yudai Matsuda^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

1 Citation (Scopus)

32 Downloads (CityUHK Scholars)

Abstract

PF1163A (1) is a fungal metabolite that inhibitssterol-C4-methyl oxidase. In this study, we identified the biosyntheticgene cluster of 1 and elucidated its biosynthetic pathway throughheterologous expression experiments. Polyketide synthase−non-ribosomal synthetase hybrid PfaA, which is responsible for thebiosynthesis of PF1163A, harbors an unusual domain organizationwith tandem condensation (C) domains and a terminal condensationdomain. Mutagenesis studies suggest that both C domains arerequired for the function of PfaA.

© 2024 The Authors. Published byAmerican Chemical Society

Original language	English
Pages (from-to)	36-40
Journal	Organic Letters
Volume	27
Issue number	1
Online published	24 Dec 2024
DOIs	https://doi.org/10.1021/acs.orglett.4c03675
Publication status	Published - 10 Jan 2025

Funding

The authors thank Prof. Katsuya Gomi (Tohoku University) and Profs. Katsuhiko Kitamoto and Jun-ichi Maruyama (University of Tokyo) for the expression vectors and fungal strain. The authors are also grateful to Dr. Kwok Chung Law (City University of Hong Kong) for the acquisition of the NMR spectra. This work was supported by General Research Fund grants from the Research Grants Council of Hong Kong (Projects 11301321 and 11309022 to Y.M.). Open Access made possible with partial support from the Open Access Publishing Fund of the City University of Hong Kong.

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abstract = "PF1163A (1) is a fungal metabolite that inhibitssterol-C4-methyl oxidase. In this study, we identified the biosyntheticgene cluster of 1 and elucidated its biosynthetic pathway throughheterologous expression experiments. Polyketide synthase−non-ribosomal synthetase hybrid PfaA, which is responsible for thebiosynthesis of PF1163A, harbors an unusual domain organizationwith tandem condensation (C) domains and a terminal condensationdomain. Mutagenesis studies suggest that both C domains arerequired for the function of PfaA.{\textcopyright} 2024 The Authors. Published byAmerican Chemical Society",

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Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A. / Ji, Qiaolin ; Wei, Xingxing; Liu, Shengkun et al.
In: Organic Letters, Vol. 27, No. 1, 10.01.2025, p. 36-40.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

AU - Ji, Qiaolin

AU - Wei, Xingxing

AU - Liu, Shengkun

AU - Matsuda, Yudai

PY - 2025/1/10

Y1 - 2025/1/10

N2 - PF1163A (1) is a fungal metabolite that inhibitssterol-C4-methyl oxidase. In this study, we identified the biosyntheticgene cluster of 1 and elucidated its biosynthetic pathway throughheterologous expression experiments. Polyketide synthase−non-ribosomal synthetase hybrid PfaA, which is responsible for thebiosynthesis of PF1163A, harbors an unusual domain organizationwith tandem condensation (C) domains and a terminal condensationdomain. Mutagenesis studies suggest that both C domains arerequired for the function of PfaA.© 2024 The Authors. Published byAmerican Chemical Society

AB - PF1163A (1) is a fungal metabolite that inhibitssterol-C4-methyl oxidase. In this study, we identified the biosyntheticgene cluster of 1 and elucidated its biosynthetic pathway throughheterologous expression experiments. Polyketide synthase−non-ribosomal synthetase hybrid PfaA, which is responsible for thebiosynthesis of PF1163A, harbors an unusual domain organizationwith tandem condensation (C) domains and a terminal condensationdomain. Mutagenesis studies suggest that both C domains arerequired for the function of PfaA.© 2024 The Authors. Published byAmerican Chemical Society

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DO - 10.1021/acs.orglett.4c03675

M3 - RGC 21 - Publication in refereed journal

SN - 1523-7060

VL - 27

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EP - 40

JO - Organic Letters

JF - Organic Letters

IS - 1

ER -

Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

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GRF: Global Genome Mining for Unexploited Bioactive Natural Products in Filamentous Fungi

GRF: Broadening the Chemical Space of Fungal Meroterpenoids and the Enzymatic Repertoire for Their Biosynthesis

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