Benzodiazepine Biosynthesis in Streptomyces refuineus

Yunfeng Hu, Vanessa Phelan, Ioanna Ntai, Chris M. Farnet, Emmanuel Zazopoulos, Brian O. Bachmann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Anthramycin is a benzodiazepine alkaloid with potent antitumor and antibiotic activity produced by the thermophilic actinomycete Streptomyces refuineus sbsp. thermotolerans. In this study, the complete 32.5 kb gene cluster for the biosynthesis of anthramycin was identified by using a genome-scanning approach, and cluster boundaries were estimated via comparative genomics. A λ-RED-mediated gene-replacement system was developed to provide supporting evidence for critical biosynthetic genes and to validate the boundaries of the proposed anthramycin gene cluster. Sequence analysis reveals that the 25 open reading frame anthramycin cluster contains genes consistent with the biosynthesis of the two halves of anthramycin: 4 methyl-3-hydroxyanthranilic acid and a "dehydroproline acrylamide" moiety. These nonproteinogenic amino acid precursors are condensed by a two-module nonribosomal peptide synthetase (NRPS) terminated by a reductase domain, consistent with the final hemiaminal oxidation state of anthramycin.

Original languageEnglish (US)
Pages (from-to)691-701
Number of pages11
JournalChemistry and Biology
Issue number6
StatePublished - Jun 25 2007



ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Benzodiazepine Biosynthesis in Streptomyces refuineus'. Together they form a unique fingerprint.

Cite this