Abstract
Actinomycetes are a representative group of bacteria that inhabit soil; in particular, Streptomyces coelicolor M511 produces actinorhodin and undecylprodiginine. Among them, undecylprodiginine has antibiotic and immunosuppression activity and is a secondary metabolite with high potential applications in biotechnological and pharmaceutical fields. High temperature stress (37 °C) reduced the biosynthesis of undecylprodiginine and induced specific branched chain alkylprodiginine derivatives, compared with the optimal growth temperature (30 °C). Also, the stress stimulated the synthesis of straight-chain FA for enhancing membrane rigidity. The inhibition of undecylprodiginine biosynthesis under high temperature stress seems to be induced by the heat sensitivity of the RedP enzyme, and this inhibition is compensated by FAS FabH. Since FabH, a homologue of RedP, has a broader substrate specificity, it leads to the production of methylundecylprodiginine and methyldodecylprodiginine. The external addition of isoleucine (as well as that of leucine and valine to a far lesser extent) enhances the synthesis of these derivatives since isoleucine catabolism generates precursors used for the biosynthesis of these compounds. These findings reveal temperature-dependent changes in precursor utilization and prodiginine diversity, providing insights into metabolic plasticity and strategies establishing a foundation for secondary metabolite derivatives engineering strategies through precursor supplementation or temperature regulation.