Details
| Original language | English |
|---|---|
| Pages (from-to) | 17988-17996 |
| Number of pages | 9 |
| Journal | Journal of the American Chemical Society |
| Volume | 130 |
| Issue number | 52 |
| Publication status | Published - 31 Dec 2008 |
| Externally published | Yes |
Abstract
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.
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- General Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemical Engineering(all)
- Colloid and Surface Chemistry
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In: Journal of the American Chemical Society, Vol. 130, No. 52, 31.12.2008, p. 17988-17996.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the entomopathogenic fungus beauveria bassiana
AU - Halo, Laura M.
AU - Heneghan, Mary N.
AU - Yakasai, Ahmed A.
AU - Song, Zhongshu
AU - Williams, Katherine
AU - Bailey, Andrew M.
AU - Cox, Russell J.
AU - Lazarus, Colin M.
AU - Simpson, Thomas J.
PY - 2008/12/31
Y1 - 2008/12/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58849158396&partnerID=8YFLogxK
U2 - 10.1021/ja807052c
DO - 10.1021/ja807052c
M3 - Article
C2 - 19067514
AN - SCOPUS:58849158396
VL - 130
SP - 17988
EP - 17996
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 52
ER -