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Marine Drugs
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Advances in Secondary Metabolites from Mangrove Holobiont
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Advances in Secondary Metabolites from Mangrove Holobiont

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Chemoecology for Drug Discovery".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 6567

Special Issue Editors

Prof. Dr. Xuefeng Zhou

E-Mail Website
Guest Editor
Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
Interests: marine natural product chemistry; drug leads; pharmacological mechanism; marine microorganisms; biotransformation
Special Issues, Collections and Topics in MDPI journals
Dr. Huaming Tao

E-Mail Website
Guest Editor
Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
Interests: marine natural products; natural product synthesis; active skeleton synthesis methodology; pharmacological mechanism

Special Issue Information

Dear Colleagues,                

Mangroves are complex and unique ecosystems, and their holobiont includes the close connections among various organisms, such as mangrove plants, microorganisms (such as fungi, bacteria, etc.), and animals. Through the study of secondary metabolites from mangrove holobionts, it is possible to gain an in-depth understanding of the ways in which these symbionts communicate and interact through chemical signal molecules. The natural products in mangrove holobionts often have unique chemical structures and diverse biological activities. Many compounds isolated from mangrove-related microorganisms have been found to have pharmacological activities, such as antibacterial, antiviral, anti-tumor, and anti-inflammatory, providing rich lead compound resources for the research and development of new drugs. These natural products have special biosynthetic mechanisms that are different from those of terrestrial organisms. Studying their synthetic pathways can discover new chemical reactions, enzymatic catalytic mechanisms, etc., providing new ideas for the development of disciplines, such as bio-organic chemistry and synthetic biology and inspiring researchers to synthesize complex compounds with application value through bionic synthesis and other means.

Prof. Dr. Xuefeng Zhou
Dr. Huaming Tao
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mangrove holobiont
  • natural products
  • pharmacological activities
  • biosynthetic mechanisms
  • symbionts communicate
  • lead compound

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Related Special Issues

Published Papers (5 papers)

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Research

21 pages, 4254 KB  
Article
“Hyphae Intertwined, Biomolecules Co-Born”—New 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
by Ting Feng, Xiaojing Li, Zhenyi Liang and Jing Xu
Mar. Drugs 2025, 23(12), 452; https://doi.org/10.3390/md23120452 - 26 Nov 2025
Cited by 1 | Viewed by 875
Abstract
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 [...] Read more.
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 (2–6, 8–13), 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 4–6 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. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)
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10 pages, 1678 KB  
Communication
Two New Chromone Derivatives from a Marine Algicolous Fungus Aspergillus versicolor GXIMD 02518 and Their Osteoclastogenesis Inhibitory Activity
by Xin Qi, Zhen Li, Miaoping Lin, Humu Lu, Shuai Peng, Huangxue Qin, Yonghong Liu, Chenghai Gao and Xiaowei Luo
Mar. Drugs 2025, 23(11), 429; https://doi.org/10.3390/md23110429 - 7 Nov 2025
Cited by 1 | Viewed by 819
Abstract
Two new chromone derivatives, cnidimols I and J (1 and 2), together with ten known aromatic derivatives (3–12), were isolated from the Beibu Gulf algicolous fungus Aspergillus versicolor GXIMD 02518. Their structures were determined by comprehensive physicochemical [...] Read more.
Two new chromone derivatives, cnidimols I and J (1 and 2), together with ten known aromatic derivatives (3–12), were isolated from the Beibu Gulf algicolous fungus Aspergillus versicolor GXIMD 02518. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations of 1 and 2 were accomplished by ECD calculations and X-ray diffraction analysis. Compound 1 was obtained as a pair of enantiomers, which were separated by chiral-phase HPLC analysis. Notably, 3,7-dihydroxy-1,9-dimethyldibenzofuran (6) displayed significant inhibition in LPS-induced NF-κB luciferase activity in RAW 264.7 macrophages, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophage cells. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)
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12 pages, 877 KB  
Article
New Polyketide and Butenolide Derivatives from the Mangrove Fungus Aspergillus spelaeus SCSIO 41433
by Zimin Xiao, Jiaqi Liang, Chun Yang, Jian Cai, Bin Yang, Xuefeng Zhou, Jie Yuan and Huaming Tao
Mar. Drugs 2025, 23(6), 251; https://doi.org/10.3390/md23060251 - 13 Jun 2025
Cited by 4 | Viewed by 1370
Abstract
Two new racemic mixtures, including a polyketide, (±)-penilactone F (1), and a butenolide, (±) phenylbutyrolactone IIa (2), were isolated from the mangrove sediment-derived strain Aspergillus spelaeus SCSIO 41433. Additionally, 20 known compounds were isolated, including four penicillin-like compounds ( [...] Read more.
Two new racemic mixtures, including a polyketide, (±)-penilactone F (1), and a butenolide, (±) phenylbutyrolactone IIa (2), were isolated from the mangrove sediment-derived strain Aspergillus spelaeus SCSIO 41433. Additionally, 20 known compounds were isolated, including four penicillin-like compounds (11–14), three alkaloids (15–17), one sesquiterpene (18), and four phenolic acids (19–22). Their structures were elucidated through NMR spectroscopy, HRESIMS, X-ray diffraction, and ECD calculations. In the PDE4 inhibitory activity and anticancer cell activity assays, compounds 2, 3, 5, 8, 9, 11–14, and 16 exhibited weak PDE4 inhibitory activity at a concentration of 10 µM, Compound 11 demonstrated potent inhibitory effects against six cancer cell lines (MDA-MB-231, MDA-MB-435, HCT116, SNB-19, PC3, and A549), with IC50 values ranging from 3.4 to 23.7 µM. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)
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12 pages, 1750 KB  
Article
Catechol Siderophores from a Mangrove-Derived Bacteria Serratia marcescens F2-2 and Their Cytotoxic Activity
by Gang Zhang, Xunming Wang, Xingwang Zhang, Lin Ye, Longyang Ke, Shimin Fan, Xuan Hong, Guoqiang Li, Bingye Yang and Lianzhong Luo
Mar. Drugs 2025, 23(6), 241; https://doi.org/10.3390/md23060241 - 30 May 2025
Cited by 1 | Viewed by 1448
Abstract
Serratia marcescens is a common Gram-negative and facultative anaerobic bacillus that produces serratiochelins with several bioactivities. In this study, four catechol siderphores (1–4), including two new ones named serratiochelins E (1) and F (2), were [...] Read more.
Serratia marcescens is a common Gram-negative and facultative anaerobic bacillus that produces serratiochelins with several bioactivities. In this study, four catechol siderphores (1–4), including two new ones named serratiochelins E (1) and F (2), were obtained from the fermentation of a mangrove-derived bacterium, S. marcescens F2-2. The structures were elucidated with various spectroscopic methods such as NMR and HR-ESI-MS. Absolute and geometric configurations of the new compounds were established by employing quantum NMR calculations in conjunction with DP4+ probability analysis, ECD calculations, and the advanced Marfey’s method. The bioactivity test showed that serratiochelin B (3) displayed weak but selective cytotoxicity against HepG2 cancer cells with an IC50 of 50.6 μmol/L and could trigger apoptosis through both Bcl-2/Bax/caspase-3 and Fas/FasL/caspase-8 signaling pathways. These findings deepen the understanding of siderophores of S. marcescens and provide a lead for research on anti-liver cancer drugs. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)
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15 pages, 3835 KB  
Article
New Bioactive Polyketides from the Mangrove-Derived Fungus Daldinia eschscholzii HJX1P2
by Miao Yu, Yikang Qiu, Shiji Chen, Jueying Shi, Xiu Gong, Jiayi Feng, Fangru Lin, Weinv Zeng, Wenyuan Kang, Caijuan Zheng and Guolei Huang
Mar. Drugs 2025, 23(6), 238; https://doi.org/10.3390/md23060238 - 30 May 2025
Viewed by 1472
Abstract
Three new naphthalene–chroman dimer derivatives, daldinaphchromes A–C (1–3), two new chroman derivatives, daldichromes A (5) and B (6), along with five known compounds (4, 7–10) were isolated from the mangrove-derived [...] Read more.
Three new naphthalene–chroman dimer derivatives, daldinaphchromes A–C (1–3), two new chroman derivatives, daldichromes A (5) and B (6), along with five known compounds (4, 7–10) were isolated from the mangrove-derived fungus Daldinia eschscholzii HJX1P2. Their structures and stereochemistries were elucidated through detailed NMR and MS analyses, calculated electronic circular dichroism, and comparison with previously reported data. Compound 1 demonstrated inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, with an IC50 value of 62.9 µM, and more effectively suppressed the expression of interleukin (IL)-6 than dexamethasone. A further mechanistic study suggested that 1 could prohibit the expression of iNOS in RAW 264.7 cells, and the molecular docking study suggested a possible interaction between 1 and the iNOS protein. Compounds 7 and 8 exhibited moderate to potent DPPH radical scavenging activity, with IC50 values of 117.4 and 46.2 µM, respectively, compared with the positive control ascorbic acid (IC50 = 45.6 µM). Compounds 4 and 10 showed ABTS+ radical scavenging activity, with IC50 values of 66.6 and 33.2 µM, respectively, which were equal to or lower than that of the positive control vitamin C (IC50 = 59.7 µM). Compounds 1–3, 7, and 9 showed antibacterial activity against three Staphylococcus aureus strains, with MIC values of 74.4–390.6 μM. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)
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