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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Genome Mining and Heterologous Reconstitution of a PKS-NRPS Gene Cluster from Aspergillus flavipes LY1-5 Affords Structurally Novel Tetronates

by
Quan Dai
1,
Yiqiao Li
1,
Shuzhe Lv
1,
Shuang Zhao
1,
Liyuan Han
1,
Jiaxin Xu
1,
Hui Shuai
2,3,
Youming Zhang
1,4,* and
Fu Yan
1,5,*
1
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
2
State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 276005, China
3
Rizhao Marine Biotechnology Center, Rizhao Polytechnic, Rizhao 276826, China
4
Shenzhen Key Laboratory of Genome Manipulation and Biosynthesis, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
5
Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life Science, Hunan Normal University, Changsha 410081, China
*
Authors to whom correspondence should be addressed.
J. Fungi 2026, 12(1), 28; https://doi.org/10.3390/jof12010028 (registering DOI)
Submission received: 29 November 2025 / Revised: 23 December 2025 / Accepted: 26 December 2025 / Published: 29 December 2025
(This article belongs to the Special Issue Fungal Metabolomics and Genomics, 2nd Edition)
Versions Notes

Abstract

Heterologous expression of silent biosynthetic gene clusters represents a key strategy for the discovery of structurally novel natural products. In this study, we obtained ten new tetronate natural products, designated as talactones A–J (1–10), through heterologous expression of a polyketide synthase–nonribosomal peptide synthetase (PKS-NRPS) gene cluster (tho) from the fungus Aspergillus flavipes LY1-5 in A. nidulans A1145. Their structures were elucidated by comprehensive HR-ESI-MS and NMR analyses. Notably, talactone A (1) contains a rare 1,4-thiazepane scaffold, whereas talactones B (2) and C (3) feature a novel 2,3-dihydrofuro [3,4-b]pyridine-4,5(1H,7H)-dione skeleton. Biosynthetic investigations indicate that the 1,4-thiazepane ring in 1 arises from a non-enzymatic reaction between a tetronate acid and cysteine, while 2 and 3 are derived from 5 and 6, respectively, via spontaneous intramolecular cyclization under acidic conditions. Antibacterial activity assays revealed that compounds 1–3, 9, and 10 exhibit moderate antibacterial effects.
Keywords: tetronate; Aspergillus flavipes LY1-5; heterologous expression; talactones A–J; antibacterial activity tetronate; Aspergillus flavipes LY1-5; heterologous expression; talactones A–J; antibacterial activity

Share and Cite

MDPI and ACS Style

Dai, Q.; Li, Y.; Lv, S.; Zhao, S.; Han, L.; Xu, J.; Shuai, H.; Zhang, Y.; Yan, F. Genome Mining and Heterologous Reconstitution of a PKS-NRPS Gene Cluster from Aspergillus flavipes LY1-5 Affords Structurally Novel Tetronates. J. Fungi 2026, 12, 28. https://doi.org/10.3390/jof12010028

AMA Style

Dai Q, Li Y, Lv S, Zhao S, Han L, Xu J, Shuai H, Zhang Y, Yan F. Genome Mining and Heterologous Reconstitution of a PKS-NRPS Gene Cluster from Aspergillus flavipes LY1-5 Affords Structurally Novel Tetronates. Journal of Fungi. 2026; 12(1):28. https://doi.org/10.3390/jof12010028

Chicago/Turabian Style

Dai, Quan, Yiqiao Li, Shuzhe Lv, Shuang Zhao, Liyuan Han, Jiaxin Xu, Hui Shuai, Youming Zhang, and Fu Yan. 2026. "Genome Mining and Heterologous Reconstitution of a PKS-NRPS Gene Cluster from Aspergillus flavipes LY1-5 Affords Structurally Novel Tetronates" Journal of Fungi 12, no. 1: 28. https://doi.org/10.3390/jof12010028

APA Style

Dai, Q., Li, Y., Lv, S., Zhao, S., Han, L., Xu, J., Shuai, H., Zhang, Y., & Yan, F. (2026). Genome Mining and Heterologous Reconstitution of a PKS-NRPS Gene Cluster from Aspergillus flavipes LY1-5 Affords Structurally Novel Tetronates. Journal of Fungi, 12(1), 28. https://doi.org/10.3390/jof12010028

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