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.