Genome Mining Reveals a Multiproduct Sesterterpenoid Biosynthetic Gene Cluster in Aspergillus ustus

Jingjing Guo; You-Sheng Cai; Fangcai Cheng; Chenjie Yang; Wenqi Zhang; Wulin Yu; Jingjing Yan; Zixin Deng; Kui Hong

doi:10.1021/acs.orglett.0c03996

Genome Mining Reveals a Multiproduct Sesterterpenoid Biosynthetic Gene Cluster in Aspergillus ustus

Org Lett. 2021 Mar 5;23(5):1525-1529. doi: 10.1021/acs.orglett.0c03996. Epub 2021 Jan 22.

Authors

Jingjing Guo¹, You-Sheng Cai², Fangcai Cheng¹, Chenjie Yang¹, Wenqi Zhang¹, Wulin Yu¹, Jingjing Yan¹, Zixin Deng¹, Kui Hong¹

Affiliations

¹ Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, People's Republic of China.
² Institute of TCM and Natural Products, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, People's Republic of China.

PMID: 33480256
DOI: 10.1021/acs.orglett.0c03996

Abstract

Genome mining of Aspergillus ustus 094102 enabled the discovery of a multiproduct bifunctional terpene synthase (BTS), AuAS. Heterologous expression of AuAS led to the discovery of five new sesterterpenes, and coexpression of the upstream CYP450 monooxygenase (AuAP450) generated four new sesterterpene alcohols. Additionally, aspergilol A showed cytotoxic activities against MCF-7, MDA-MB231, and HepG2 cancer cells (IC₅₀ 21.20-48.76 μM), and aspergilol B exhibited a cytotoxic effect on MCF-7 cells (IC₅₀ 27.41 μM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aspergillus / chemistry*
Humans
MCF-7 Cells
Molecular Structure
Multigene Family
Sesterterpenes / chemistry
Sesterterpenes / metabolism*

Substances

Sesterterpenes

Supplementary concepts

Aspergillus ustus