{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T21:37:44Z","timestamp":1783460264678,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82160675"],"award-info":[{"award-number":["82160675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973229"],"award-info":[{"award-number":["81973229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Research Program of Hainan Province","award":["ZDYF2021SHFZ108"],"award-info":[{"award-number":["ZDYF2021SHFZ108"]}]},{"name":"Collaborative Innovation Center Foundation of Hainan University","award":["XTCX2022STB01"],"award-info":[{"award-number":["XTCX2022STB01"]}]},{"name":"Guangdong Key Laboratory of Marine Materia Medica Open Fund","award":["LMM2021-4"],"award-info":[{"award-number":["LMM2021-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The co-culture technique, mimicking natural microbial interactions, has proven to be successful at activating silent biosynthetic gene clusters (BGCs) to produce novel metabolites or enhance the yield of specific metabolites. To effectively decode induction processes, it is critical to have a comprehensive understanding of intermicrobial interactions across both volatile and non-volatile metabolomes. As part of our attempt to uncover structurally unique and biologically active natural products from mangrove endophytic fungi, Phomopsis asparagi DHS-48 was co-cultured with another mangrove fungal strain, Pestalotiopsis sp. HHL-101. The competition interaction of the two strains was investigated using morphology and scanning electron microscopy (SEM), and it was discovered that the mycelia of the DHS-48 and HHL-101 compressed and tangled with each other in the co-culture system, forming an interwoven pattern. To profile volatile-mediated chemical interactions during fungal co-culture, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) coupled with orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted. Meanwhile, non-volatile metabolites from both liquid and solid small-scale co-cultures were profiled via HPLC. Two new polyketides, named phaseolorin K (1) and pestaphthalide C (7), together with 11 known compounds (2\u20136, 8\u201313), were characterized from solid-state co-cultivation extracts of these two titled strains. Their planar structures were established by analysis of HRMS, MS\/MS, and NMR spectroscopic data, while absolute configurations were assigned using ECD calculations. Co-culture feeding experiments demonstrated that DHS-48 exerts antagonistic activity against HHL-101 through altering its hyphal morphology, which mediated enhanced biosynthesis of non-volatile antimicrobial metabolites 5 and 6. Biological assays revealed that compounds 4\u20136 exhibited potent in vitro cytotoxicity against human cancer cell lines HeLa and HepG2, compared to the positive controls adriamycin and fluorouracil. Compound 2 moderately inhibited the proliferation of ConA-induced T and LPS-induced B murine spleen lymphocytes.<\/jats:p>","DOI":"10.3390\/md23120452","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["\u201cHyphae Intertwined, Biomolecules Co-Born\u201d\u2014New Polyketides Induction by Co-Culture of the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48 and Pestalotiopsis sp. HHL-101 at Both Volatile and Non-Volatile Levels"],"prefix":"10.3390","volume":"23","author":[{"given":"Ting","family":"Feng","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Liang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6201-5318","authenticated-orcid":false,"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1039\/C4RA11756E","article-title":"Bioactive natural products derived from mangrove-associated microbes","volume":"5","author":"Xu","year":"2015","journal-title":"RSC Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.2174\/092986711798184307","article-title":"Biomolecules produced by mangrove-associated microbes","volume":"18","author":"Xu","year":"2011","journal-title":"Curr. 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