Pyrrolylpolyenes from fungi: biosynthesis and analogue production

Rumbrin is a fungal pyrrolylpolyene which possesses an unusual structure and both cytotoxic and cytoprotective activities [1]. Addition of halide salts to the culture medium of a rumbrin-producing Gymnoascus reessii strain resulted in an altered production profile: NaCl increased production of chloropolyenylpolyenes, while NaBr led to the production of brominated and dechlorinated polyenes. [2] Two of these analogues, 12E-bromoisorumbrin and 12E-dechloroisorumbrin, were isolated and characterised – both possessed significantly lower cytotoxicity than rumbrin. Feeding studies with another producing fungus, Auxarthron umbrinum, offered insights into the biosynthesis of rumbrin. Stable-isotope labelled acetate, proline and methionine showed good incorporation into the polyene products, as determined by MS analysis. In label dilution studies, pyrrole-2-carboxylate drastically decreased the amount of ¹⁵N-proline incorporated into the polyenes and increased levels of polyene production, indicating that it is a direct intermediate in the biosynthesis of rumbrin. A possible mechanism for rumbrin biosynthesis is outlined.

Acknowledgements: IRCSET, University of Queensland.

References: 1. Yamaguchi, Y. et al. (1993)J. Antibiot. 46:888–891.

2.. Clark, B. R et al. (2007)J. Nat. Prod. 70:665–667.