Pangenomics and Comparative Biosynthetic Diversity of Malaysian Mangrove-Derived Streptomyces albidoflavus MUM256 among S. albidoflavus-Assigned Genomes

Abstract

Streptomyces sp. MUM256, isolated from Malaysian mangrove soil, has previously shown antioxidant and selective anticancer activities, including induction of cell-cycle arrest and apoptosis in colon cancer cells. However, its precise taxonomic position and biosynthetic potential remained unresolved at the whole-genome and population levels. Here, we sequenced a high-quality long-read genome of MUM256 and integrated genome-based taxonomy, pangenomics and comparative biosynthetic gene cluster (BGC) analysis. The final assembly comprised a single 6.89-Mb contig with 73.4% G+C content, 98.5% BUSCO completeness and 5,897 predicted protein-coding sequences. Genome-based analyses consistently assigned MUM256 to Streptomyces albidoflavus, with NRRL B-1271 identified as its closest GTDB-Tk placement reference. A quality-filtered cohort of 151 genomes revealed an open pangenome comprising 21,082 gene clusters, including 2,684 strict-core clusters, with continued gene-family accumulation supported by Heaps' law modelling (γ = 0.307). Population-scale genome mining of 119 quality-filtered genomes identified 2,651 BGC records grouped into 178 gene cluster families (GCFs), of which 84.3% were rare or singleton. MUM256 contained 18 predicted BGCs representing 18 GCFs, all shared with other members of the analysed S. albidoflavus-assigned genomes. Comparative analysis of fredericamycin A-like and SF2768-like loci further revealed population-level variation in BGC prevalence and architecture. Together, these findings establish MUM256 as S. albidoflavus and provide a population-genomic framework for prioritising biosynthetic loci for future metabolomic and functional validation.