A Structural Analysis of the Angucycline-Like Antibiotic Auricin from Streptomyces lavendulae Subsp. Lavendulae CCM 3239 Revealed Its High Similarity to Griseusins

Abstract

We previously identified the <i>aur1</i> gene cluster in <i>Streptomyces lavendulae</i> subsp. <i>lavendulae</i> CCM 3239 (formerly <i>Streptomyces aureofaciens</i> CCM 3239), which is responsible for the production of the angucycline-like antibiotic auricin (<b>1</b>). Preliminary characterization of <b>1</b> revealed that it possesses an aminodeoxyhexose d-forosamine and is active against Gram-positive bacteria. Here we determined the structure of <b>1</b>, finding that it possesses intriguing structural features, which distinguish it from other known angucyclines. In addition to d-forosamine, compound <b>1</b> also contains a unique, highly oxygenated aglycone similar to those of spiroketal pyranonaphthoquinones griseusins. Like several other griseusins, <b>1</b> also undergoes methanolysis and displays modest cytotoxicity against several human tumor cell lines. Moreover, the central core of the <i>aur1</i> cluster is highly similar to the partial <i>gris</i> gene cluster responsible for the biosynthesis of griseusin A and B in both the nature of the encoded proteins and the gene organization.