Hitachimycin

Hitachimycin (also known as stubomycin) is a bicyclic macrolactam antibiotic produced by Streptomyces species. It contains an (S)-?-phenylalanine starter unit incorporated into a polyketide backbone via a ?-amino acid-selective adenylation enzyme (HitB). Post-polyketide synthase (post-PKS) tailoring enzymes construct the unique bicyclic macrolactam scaffold through reduction and methylation steps. Biologically, hitachimycin exhibits growth inhibitory activity against Gram-positive bacteria and transplantable murine tumors, including Ehrlich carcinoma and leukemia P388, and shows direct cytotoxicity against HeLa cells in vitro. Mutasynthesis and enzyme engineering studies indicate that structural modifications alter biological activity, suggesting interaction with cellular targets involved in proliferation.