Genome mining of amylases and amylase inhibitors from Streptomyces

Most antibiotics are derived from Streptomyces bacteria and produced industrially via fermentations relying on food-grade feedstocks, which have a substantial environmental impact. Efficient utilization of starch-rich organic wastes, such as bread and potato waste, as alternative feedstocks, remains limited by incomplete knowledge of starch metabolism in Streptomyces. Here, a genus-wide analysis of 295 Streptomyces strains was performed, identifying 645 amylases grouped into pullulanases, α-1,4-amylases and cyclomaltodextrin-like amylases, alongside biosynthetic gene clusters encoding amylase inhibitors such as acarbose and tendamistat. Structural and sequence analyses revealed that inhibitor resistance may arise from subtle modifications in the α-amylase catalytic pocket. This comprehensive analysis of amylases and inhibitors provides a foundation for engineering inhibitor-resistant enzymes tailored to diverse starch substrates, facilitating the development of sustainable, starch-based Streptomyces fermentations.