Pyrrolo[1,4]benzodiazepines(PBDs), produced by actinomycetes, are sequence selective DNA alkylating agentswith anti-tumor and antibiotic properties. Sibiromycin and tomaymycin are twonaturally produced PBDs. Sibiromycin is the most potent naturally produced PBDsand only one of two available glycosylated PBDs. Tomaymycin was used as thetemplate for SJG-136, a synthetic PBD dimer. Phase I clinical trials of SJG-136have been successful for the treatment of metastatic or unresectable solidtumors. We have identified and sequenced the tomaymycin and sibiromycin geneclusters. Progress made on the elucidation of the biosynthesis of thesecompounds and on the production of PBDs analogs will be discussed.

Deciphering the biosynthesis of pyrrolobenzodiazepines and bioengineering production of their analogs

239th National Meeting (2010)

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