Identification of the Bacterial Maytansinoid GeneCluster asc Provides Insights into the Post-PKS Modificationsof Ansacarbamitocin Biosynthesis

A new biosynthetic gene cluster for the bacterial maytansinoids, ansacarbamitocins (ASCs), was identified in Amycolatopsis alba DSM 44262. The post-PKS modifications of ASCs were elucidated on the basis of bioinformatics analysis. Specific gene disruption and heterologous expression led to the isolation of seven new bacterial maytansinoids. The 3′-O-methyltransferase and 3-O-carbamyltransferase involved in bacterial maytansinoid biosynthesis were identified for the first time. The new bacterial maytansinoids 7 and 13 showed strong antitumor activities against four human cancer cell lines.