Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743

摘要: Ecteinascidin 743 (ET-743, Yondelis) is a clinically approved chemotherapeutic natural product isolated from the Caribbean mangrove tunicate Ecteinascidia turbinata. Researchers have long suspected that microorganism may be true producer of anticancer drug, but its genome has remained elusive due to our inability culture bacterium in laboratory using standard techniques. Here, we sequenced and assembled complete ET-743 producer, Candidatus Endoecteinascidia frumentensis, directly metagenomic DNA tunicate. Analysis ∼ 631 kb microbial revealed strong evidence an endosymbiotic lifestyle extreme reduction. Phylogenetic analysis suggested anti-cancer drug taxonomically distinct other microorganisms could represent new family Gammaproteobacteria. The also greatly expanded understanding production biosynthetic genes dispersed across more than 173 small genome. gene cluster's architecture preservation demonstrate likely essential interactions with host. Taken together, these studies elucidate unique, pharmaceutically important highlight wide diversity bacteria capable making potent products.