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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microbiotechnology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1593027

This article is part of the Research TopicExploration of Marine Microorganisms for Sustainable BiotechnologyView all 3 articles

Deletion of a Polyketide Synthase PhoE Induces Monoterpenes Production in Ascidian-Derived fungus Diaporthe sp. SYSU-MS4722

Provisionally accepted
Siwen YuanSiwen Yuan1Shitao ZhuangShitao Zhuang2Han YanhongHan Yanhong2Senhua ChenSenhua Chen3Senhua ChenSenhua Chen3Qifeng LiuQifeng Liu3,4Yan YanYan Yan2*Zhizeng GaoZhizeng Gao3*Qilin WuQilin Wu1*
  • 1Department of Bioengineering, Zunyi Medical University, Zhuhai, Guangdong Province, China
  • 2Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China;, Zhuhai, China
  • 3School of Marine Sciences, Sun Yat-sen University, Zhuhai 519082, China;, Zhuhai, China
  • 4Shenzhen Lions King Hi-Tech Co., Ltd, Shenzhen 518000, China, Shenzhen, China

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Marine-derived fungi represent an underexplored source of monoterpenes, with only sporadic reports over the past two decades, making their discovery particularly challenging. Whole-genome sequencing of Diaporthe sp. SYSU-MS4722, an ascidian-derived fungus isolated from Styela plicata, identified 130 biosynthetic gene clusters (BGCs), underscoring its vast biosynthetic potential. However, previous studies demonstrated that Diaporthe sp. SYSU-MS4722 predominantly produces xanthone phomoxanthone A under standard laboratory conditions, suggesting that many BGCs remain cryptic. Notably, 16 of these BGCs encode terpene synthase genes, indicating the potential for monoterpene biosynthesis. To activate these silent BGCs and discover monoterpenes, we deleted the polyketide synthase (PKS) gene phoE, responsible for phomoxanthone A biosynthesis, generating the mutant strain Diaporthe sp. SYSU-MS4722△phoE, from which three new monoterpenes, diaporterpenes D-F (1-3), three known monoterpenes (4-6), and two new polypropionate derivatives, diaporpolypropionate A (7) and diaporpolypropionate B (8), were isolated. Compounds 1, 4, 7, and 8 were evaluated for their cytotoxicity and anti-inflammatory effects in human non-small cell lung cancer A549 cells. Compound 1 exhibited cytotoxic activity with an IC50 value of 89.33 μM. Compounds 4 and 7 demonstrated anti-inflammatory activity, as measured by an ELISA assay assessing the inhibition of IL-6 secretion, with EC50 values of 41.85 μM and 70.80 μM, respectively.

Keywords: genome mining, Monoterpenes, Polypropionate derivatives, Phomoxanthone A, Antiinflammatory activity

Received: 13 Mar 2025; Accepted: 10 Jun 2025.

Copyright: © 2025 Yuan, Zhuang, Yanhong, Chen, Chen, Liu, Yan, Gao and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yan Yan, Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China;, Zhuhai, China
Zhizeng Gao, School of Marine Sciences, Sun Yat-sen University, Zhuhai 519082, China;, Zhuhai, China
Qilin Wu, Department of Bioengineering, Zunyi Medical University, Zhuhai, Guangdong Province, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material