# Marine endophytes: biosynthetic engines for novel bioactive metabolites

**Authors:** Cun-Cui Kong, Jia-Yi Wang, Bo-Hao Shan, Hong-Xia Zhang, Song Qin, Cheng-Gang Ren

PMC · DOI: 10.3389/fmicb.2025.1684777 · Frontiers in Microbiology · 2025-10-08

## TL;DR

This paper reviews marine endophytes as sources of valuable bioactive compounds and suggests strategies to improve their stable and scalable production for pharmaceutical use.

## Contribution

The paper proposes a strategic roadmap and novel approaches like mutagenesis and metabolic engineering to enhance metabolite production from marine endophytes.

## Key findings

- Marine endophytes produce diverse bioactive metabolites with pharmaceutical potential.
- Genomic instability and inconsistent yields limit commercial use of these metabolites.
- Strategies like fermentation tuning and metabolic engineering can improve production efficiency.

## Abstract

Marine endophytes are prolific sources of structurally diverse secondary metabolites with significant pharmaceutical potential, including anticancer, antimicrobial, and antioxidant agents. However, their commercial utilization is hindered by genomic instability in axenic cultures and inconsistent metabolite yields. While current studies focus on symbiotic interactions and compound discover, critical gaps persist in harnessing their biosynthetic capabilities. This review synthesizes knowledge on marine fungal metabolites and proposes a paradigm shift toward resource-driven research. It addresses strain improvement limitations and suggests strategies like mutagenesis, protoplast fusion, and metabolic engineering to bolster production stability and efficiency. The paper also discusses biological process optimization, including fermentation tuning, inducer and precursor addition, and adsorbent use, to enhance natural product synthesis. By identifying these research gaps and proposing a strategic roadmap, the review advances the stable and scalable production of bioactive metabolites, unlocking the commercial and therapeutic potential of marine endophytic fungi.

## Full-text entities

- **Genes:** CCK (cholecystokinin) [NCBI Gene 885], CYP2B6 (cytochrome P450 family 2 subfamily B member 6) [NCBI Gene 1555] {aka CPB6, CYP2B, CYP2B7, CYPIIB6, EFVM, IIB1}
- **Diseases:** C.flammea (OMIM:211750), cancer (MESH:D009369), cytotoxic (MESH:D064420), bacterial contamination (MESH:D001424), HS (MESH:C567159), inflammatory (MESH:D007249)
- **Chemicals:** chloramphenicol (MESH:D002701), mycoepoxydiene (MESH:C476085), iso-coumarin (MESH:D049934), indole (MESH:C030374), FDDP-E. (-), tannins (MESH:D013634), naphthoquinone (MESH:D009285), cyclic peptides (MESH:D010456), paclitaxel (MESH:D017239), lactones (MESH:D007783), decalin (MESH:C007229), tetracycline (MESH:D013752), Peptide (MESH:D010455), cyclopentanone (MESH:C007201), putrescine (MESH:D011700), peroxides (MESH:D010545), lovastatin (MESH:D008148), Polyketide (MESH:D061065), Xanthone (MESH:C009689), coumarin (MESH:C030123), glucose (MESH:D005947), chromone (MESH:D002867), diterpenes (MESH:D004224), macrolides (MESH:D018942), amino acids (MESH:D000596), xanthones (MESH:D044004), Flavonoid (MESH:D005419), NaI (MESH:D012974), quinones (MESH:D011809), saponins (MESH:D012503), proline (MESH:D011392), polyenes (MESH:D011090), Alkaloid (MESH:D000470), ayamycin (MESH:C561927), penicillin (MESH:D010406), C. (MESH:D002244), pristinamycin (MESH:D025762), anthraquinone (MESH:D000880), esters (MESH:D004952), polymer (MESH:D011108), NaOCl (MESH:D012973), ethanol (MESH:D000431), streptomycin (MESH:D013307), nucleosides (MESH:D009705), Terpenoid (MESH:D013729), Steroid (MESH:D013256), phenolic acids (MESH:C017616)
- **Species:** Aureobasidium melanogenum (species) [taxon 46634], Fucus vesiculosus (species) [taxon 49266], Phomopsis sp. (species) [taxon 1715245], Streptomyces pristinaespiralis (species) [taxon 38300], Paecilomyces variotii (species) [taxon 264951], Microsporum sp. (species) [taxon 2595038], Penicillium (genus) [taxon 5073], Aspergillus (genus) [taxon 5052], Trichoderma (genus) [taxon 5543], Fungi (kingdom) [taxon 4751], PX clade (clade) [taxon 569578], Aplosporella javeedii (species) [taxon 1346708], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12540334/full.md

## References

171 references — full list in the complete paper: https://tomesphere.com/paper/PMC12540334/full.md

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Source: https://tomesphere.com/paper/PMC12540334