Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the flavoenzyme Af12070 from Aspergillus fumigatus.

ABSTRACT: The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ) peptidyl alkaloids of increasing scaffold complexity using L-Trp, 2 equiv of L-Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ gene cluster encodes two non-ribosomal peptide synthetases (NRPS) and two flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an oxidative annulation sequence to couple alanine to the indole side chain of FQF to yield the imidazolindolone-containing FQA. In this study we show that the fourth enzyme, the monocovalent flavoprotein Af12070, introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzi

SUBMITTER: Ames BD 

PROVIDER: S-EPMC3194008 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature