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| Main Authors: | , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Marine drugs
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40422808/ |
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Table of Contents:
- The Isolation, Structural Characterization, and Biosynthetic Pathway of Unguisin from the Marine-Derived Fungus . Diao, Wenjiao Zhang, Wei Zhang, Xiaoxi Du, Siyu Zheng, Caijuan Huang, Xuenian Lu, Xuefeng Aspergillus Biosynthetic Pathways Peptides, Cyclic Multigene Family Aquatic Organisms Peptide Synthases Unguisins, a class of structurally complex cyclic peptides featuring a -aminobutyric acid residue embedded in the skeleton, exhibit diverse biological activities. Here, a new unguisin K, along with three known congeners, was isolated from the marine-derived fungus MEFC1001. The biosynthetic pathway was elucidated through gene disruption coupled with in vitro enzymatic characterization. The biosynthetic gene cluster (BGC) containing and , in conjunction with an extra-clustered gene , collaborates to synthesize these unguisins. The alanine racemase (AR) UgsC catalyzes the isomerization of Ala and provides d-Ala as the starter unit for the non-ribosomal peptide synthetase (NRPS). The unique localization of outside the BGC is different from previously reported unguisin-producing systems where AR genes reside within BGCs. The methyltransferase UgsB mediates a key pre-modification step by methylating phenylpyruvic acid to yield -methylphenylpyruvate, which is subsequently incorporated as -methylphenylalanine during NRPS assembly. This represents the first experimental evidence of the -carbon methylation of Phe residue occurring at the precursor level rather than through post-assembly modification. The NRPS UgsA recruits a variety of amino acids for assembly and cyclization to form mature unguisins. Additionally, genome mining utilizing UgsA as a query identified homologous NRPSs in diverse fungal species, highlighting the potential for unguisin production in fungi. This study enriches the biosynthetic diversity of cyclic peptides and provides guidance for exploring unguisin-like natural products derived from fungi.