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Heterologous Biosynthesis and Genomics-Driven Derivatization of Fungal Bioactive Sesterterpenoid Variecolin

08 November 2021, Version 1
Working Paper
This content is an early or alternative research output and has not been peer-reviewed by Cambridge University Press at the time of posting.

Abstract

The biosynthetic gene cluster of fungal bioactive sesterterpenoids, variecolin (1) and variecolactone (2), was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues, one of which exhibited potent anticancer activity comparable to that of 1.

Keywords

Natural product biosynthesis
Sesterterpenoids
Synthetic biology
Variecolin

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Now Published

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties [opens in a new tab]
Dexiu Yan, Jemma Arakelyan, Teng Wan, Ritvik Raina, Tsz Ki Chan, Dohyun Ahn, Vladimir Kushnarev, Tsz Kiu Cheung, Ho Ching Chan, Inseo Choi, Pui Yi Ho, Feijun Hu, Yujeong Kim, Hill Lam Lau, Ying Lo Law, Chi Seng Leung, Chun Yin Tong, Kai Kap Wong, Wing Lam Yim, Nikolay S. Karnaukhov, Richard Y.C. Kong, Maria V. Babak, Yudai Matsuda journal article
Acta Pharmaceutica Sinica B
Print publication date: Aug, 2023

Version History

Nov 08, 2021 Version 1

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The content is available under CC BY NC ND 4.0 [opens in a new tab]

DOI

10.26434/chemrxiv-2021-x171c
D O I: 10.26434/chemrxiv-2021-x171c [opens in a new tab]

Funding

Research Grants Council, University Grants Committee

Author’s competing interest statement

The author(s) have declared they have no conflict of interest with regard to this content

Ethics

The author(s) have declared ethics committee/IRB approval is not relevant to this content

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