Metabolic Blockade-Based Genome Mining Reveals Lipochain-Linked Dihydro-β-alanine Synthetases Involved in Autucedine Biosynthesis

Continuously mining the Streptomyces olivaceus SCSIO T05 genome leads to the identification of new lipopeptides (autucedines A–C), constituting members of the 10th skeleton isolated from this strain. The corresponding biosynthetic gene cluster ( aut ) was verified by heterogeneous expression, and another two analogues (autucedines D and E) were isolated from the heterogeneous expression strain. Gene inactivation experiments revealed that construction of the unique “lipochain-linked dihydro-β-alanine” unit takes place prior to the NRPS assembly line.