Valorization of seaweed hydrolysate for production of the high-value reverse antibiotic nybomycin using metabolically engineered Streptomyces explomaris

This study develops a pipeline for high-level production of the reverse antibiotic nybomycin from three seaweed species: Himanthalia elongata, Palmaria palmata, and Ulva lactuca. Screening Streptomyces strains identified S. explomaris, a marine species, as the best host to express the nybomycin gene cluster. The accumulated low yields in artificial seawater with brown seaweed hydrolysate. Gene expression analysis revealed downregulation of precursor supply pathways and upregulation of repressors, limiting biosynthesis. Metabolic engineering addressed these bottlenecks, leading to a superior S. explomaris mutant achieving 57 mg/L, a five-fold increase as compared to reported yields. The strain effectively valorized commercial seaweed hydrolysates, highlighting marine feedstocks' potential for antibiotic production. Whole transcriptomes of a nybomycin production strain derived from four time points (early exponential phase (17 h), mid-exponential phase after glucose and mannitol depletion (33 h), stationary phase after galactose and mannose exhaustion (75 h), and late phase (175 h)) and two growth conditions (chemically defined medium using either deionized water or artificial sea water as a base) using 3 biological replicates each.