Unveiling microbial secondary metabolite biosynthetic gene clusters from alkaline soda Lake Chitu, in the Ethiopian Rift Valley

Unveiling microbial secondary metabolite biosynthetic gene clusters from alkaline soda Lake Chitu, in the Ethiopian Rift Valley Microorganisms inhabiting alkalihalo-soda lakes are known for producing diverse secondary metabolites with potential biotechnological and pharmaceutical applications. This study explored the biosynthetic capabilities of microbial communities from Ethiopia’s Chitu Lake through shotgun metagenomic sequencing and metagenome-assembled genome (MAG) analyses using various bioinformatics tools. Analysis of MAGs using the Antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) revealed 13 major types of biosynthetic gene clusters. The most abundant were terpene-precursors (32%) and terpene clusters (25%), followed by ribosomally synthesized and post-translationally modified peptides (9%) and nonribosomal peptide synthetases (7%). Other less common BGCs (5% each) included betalactone, ectoine, and Type I polyketide synthase, while rare types (2% each) comprised arylpolyene, hydrogen cyanide, phosphonate, ranthipeptide, and others. The Natural Product Domain Seeker (NaPDoS) detected ketosynthase domains linked to pharmaceutically important such as various fatty acid synthesis, modular and iterative domain classes, and condensation domain which is associated with L-amino acid coupling (LCL) domain class, such as those involved in syringomycin biosynthesis. In addition, bacteriocin analysis identified sactipeptides (56%) and lasso peptides (28%) as dominant types. Kyoto Encyclopedia of Genes and Genomes pathway analysis uncovered several secondary metabolite pathways including those for penicillin, cephalosporins, alkaloids, and phenazines. Rapid Annotation using Subsystem Technology further highlighted secondary metabolism pathways vital for microbial survival in Chitu Lake’s extreme environment. The discovery of diverse biosynthetic gene cluster positions Chitu Lake as a valuable source of secondary metabolites, highlighting the biotechnological, industrial, pharmaceutical, agricultural and environmental potential of its extremophilic microbes and supporting further bioprospecting efforts. How to cite: Bekele GK, Balcha ES, Meka AF, et al. Unveiling microbial secondary metabolite biosynthetic gene clusters from alkaline soda Lake Chitu, in the Ethiopian Rift Valley. Electron J Biotechnol 2025;77. https://doi.org/10.1016/j.ejbt.2025.06.002 .