Biosynthesis of pyrrolylpolyenes in Auxarthron umbrinum

Abstract

The biosynthesis of the pyrrolylpolyene rumbrin (1) in the fungus Auxarthron umbrinum was elucidated using feeding studies with labelled precursors. Incorporation of stable isotopes from [(15)N]-proline, [(13)C]-methionine and [(13)C]-acetate confirmed that these were the precursors of the pyrrole moiety, methyl groups, and backbone of rumbrin, respectively. Label-dilution experiments with pyrrole-2-carboxylate confirmed it was a direct precursor in the biosynthesis of rumbrin. Both 3- and 4-chloropyrrolecarboxylates were also accepted as precursors in polyene production.

A labile point in mutant amphotericin polyketide synthases

“…Many of these compounds are biologically active and the polyenylpyrone group includes cytoprotectants, antioxidants, antibacterials and anticancer agents (Clark and Murphy, 2009;Coleman and Waleza, 2006). The starter unit for these polyketides is critical for activity.…”

Living on pyrrolic foundations – Advances in natural and artificial bioactive pyrrole derivatives

“…It is obtained from proline, methionine, and acetate, in a biosynthetic route of what is believed to be an iterative polyketide synthase enzyme complex. In light of its promising qualities, it would be prudent to study its, largely unknown biosynthetic pathway [64].…”

Access to High Value Natural and Unnatural Products through Hyphenating Chemical Synthesis and Biosynthesis

“…31 In the biosynthesis of rumbrin, the pyrrol-2-carboxylate starter unit is derived from proline before tethering to the PKS machinery. 32 Scheme 6 Feeding analogues of pyrrol-2-carboxylate to the rumbrin producer resulted in the generation of rumbrin analogues, which showed improved activity against various cancer cell lines 31 MacMillan's access to a diverse suite of biologically active ammosamides, using precursor-directed biosynthesis without prior need for strain engineering, demonstrates how substrate flexible some biosynthetic pathways may be. The ammosamides are amidine analogues, which belong to the alkaloid ammosamide family and are isolated from the marine microbe Streptomyces variabilis.…”