In this study, metagenomic analysis was employed to investigate the bacterial communities in the Muan tidal mudflat of the Republic of Korea. We used metagenomic analysis to identify the microbial community in tidal soil dominated by Proteobacteria. From this environment, the bacterial strain, Saccharomonospora sp. CMS18, was isolated and yielded two previously unknown compounds, penipaline D (3) and N-acetyl-dimethylallyltryptophan (4). The chemical structures of the isolated compounds along with 6-dimethylallyl-indole (1), 6-dimethylallyltryptophan (2), penipaline D (3), and N-acetyl-dimethylallyltryptophan (4) were structurally investigated using HR-ESI-MS and NMR spectroscopy. The isolated compound 6-dimethylallyl-indole (1) demonstrated broad-spectrum antifungal activity, with IC₅₀ value of 0.04 mM against Candida glabrata and 0.35 mM against both Candida albicans and Cryptococcus neoformans. Additionally, it exhibited additive interaction with caspofungin against C. albicans.

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes.