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University of Wisconsin-Madison

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Sci. Adv., Feb 23 2024, 10 (8) | https://doi.org/10.1126/sciadv.adk7416 Terpenoid balance in Aspergillus nidulans unveiled by heterologous squalene synthase expression

Sung Chul Park ¹, Breanne N Steffan ¹, Fang Yun Lim ^1,2, Raveena Gupta ³, Fatma Ayaloglu Butun ³, Hongyu Chen ⁴, Rosa Ye ⁴, Timothy Decker ⁴, Chengcang C Wu ⁴, Neil L Kelleher ³, Jin Woo Bok ^1*, Nancy P Keller ^1,5*

¹Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.

²Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

³Department of Chemistry, Northwestern University, Evanston, IL, USA.

⁴Intact Genomics Inc., St. Louis, MO, USA.

⁵Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, USA.

^*Corresponding authors: Jin Woo Bok, Nancy P Keller

Abstract

Filamentous fungi produce numerous uncharacterized natural products (NPs) that are often challenging to characterize because of cryptic expression in laboratory conditions. Previously, we have successfully isolated novel NPs by expressing fungal artificial chromosomes (FACs) from a variety of fungal species into Aspergillus nidulans. Here, we demonstrate a twist to FAC utility wherein heterologous expression of a Pseudogymnoascus destructans FAC in A. nidulans altered endogenous terpene biosynthetic pathways. In contrast to wild type, the FAC transformant produced increased levels of squalene and aspernidine type compounds, including three new nidulenes ( 1- 2, and 5), and lost nearly all ability to synthesize the major A. nidulans characteristic terpene, austinol. Deletion of a squalene synthase gene in the FAC restored wild-type chemical profiles. The altered squalene to farnesyl pyrophosphate ratio leading to synthesis of nidulenes and aspernidines at the expense of farnesyl pyrophosphate-derived austinols provides unexpected insight into routes of terpene synthesis in fungi.

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형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-27)
연구진국외 연구진
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