Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the entomopathogenic fungus Beauveria bassiana.
Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria bassiana were investigated by a combination of gene knockout, antisense RNA, and gene coexpression studies. Open reading frames (ORF) 3 and 4 of the tenellin biosynthetic gene cluster were previously shown to encode a trans-acting enoyl reductase and a hybrid polyketide synthase nonribosomal peptide synthetase (PKS-NRPS), respectively, which together synthesize the acyltetramic acid pretenellin-A. In this work, we have shown that ORF1 encodes a cytochrome P450 oxidase, which catalyzes an unprecedented oxidative ring expansion of pretenellin-A to form the 2-pyridone core of tenellin and related metabolites, and that this enzyme does not catalyze the formation of a hydroxylated precursor. Similar genes appear to be associated with PKS-NRPS genes in other fungi. ORF2 encodes an unusual cytochrome P450 monooxygenase required for the selective N-hydroxylation of the 2-pyridone which is incapable of N-hydroxylation of acyltetramic acids.
Halo
Laura M
LM
School of Chemistry, University of Bristol, Cantock's Close, Bristol, United Kingdom.
Heneghan
Mary N
MN
Yakasai
Ahmed A
AA
Song
Zhongshu
Z
Williams
Katherine
K
Bailey
Andrew M
AM
Cox
Russell J
RJ
Lazarus
Colin M
CM
Simpson
Thomas J
TJ
D001236:Aspergillus oryzae / Q000235:genetics / Q000378:metabolism; D052982:Beauveria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006900:Hydroxylation; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D010084:Oxidation-Reduction; D011728:Pyridones / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics
D011728:Pyridones; D016372:RNA, Antisense; C015528:tenellin; D009251:NADPH-Ferrihemoprotein Reductase