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Pyrrolylpolyenes from fungi: biosynthesis and analogue production
Rumbrin is a fungal pyrrolylpolyene which possesses an unusual structure and both cytotoxic and cytoprotective activities . 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.  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.
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