Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis

Stefanie B. Bumpus; Nathan A. Magarvey; Neil L. Kelleher; Christopher T. Walsh; Christopher T. Calderone

doi:10.1021/ja8040042

Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis

Stefanie B. Bumpus, Nathan A. Magarvey, Neil L. Kelleher, Christopher T. Walsh, Christopher T. Calderone

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Polyketide biosynthesis is typically directed by cis-acting catalytic domains. In the case of the Bacillus subtilis secondary metabolite dihydrobacillaene, the cis-acting domains are not sufficient to generate the saturated C14′-C15′ bond. In this communication, we identify PksE as a trans-acting enoyl reductase utilized in the biosynthesis of this portion of dihydrobacillaene. PksE is homologous to the enzymes predicted to serve as enoyl reductases in polyunsaturated fatty acid (PUFA) biosynthesis, and we confirmed this functional assignment in vitro. These results suggest a general enoyl reduction pathway in polyketide biosynthesis and a means by which PUFA-like biosynthetic machinery can modulate small-molecule function.

Original language	English (US)
Pages (from-to)	11614-11616
Number of pages	3
Journal	Journal of the American Chemical Society
Volume	130
Issue number	35
DOIs	https://doi.org/10.1021/ja8040042
State	Published - Sep 3 2008

Funding

ASJC Scopus subject areas

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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abstract = "Polyketide biosynthesis is typically directed by cis-acting catalytic domains. In the case of the Bacillus subtilis secondary metabolite dihydrobacillaene, the cis-acting domains are not sufficient to generate the saturated C14′-C15′ bond. In this communication, we identify PksE as a trans-acting enoyl reductase utilized in the biosynthesis of this portion of dihydrobacillaene. PksE is homologous to the enzymes predicted to serve as enoyl reductases in polyunsaturated fatty acid (PUFA) biosynthesis, and we confirmed this functional assignment in vitro. These results suggest a general enoyl reduction pathway in polyketide biosynthesis and a means by which PUFA-like biosynthetic machinery can modulate small-molecule function.",

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T1 - Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis

AU - Bumpus, Stefanie B.

AU - Magarvey, Nathan A.

AU - Kelleher, Neil L.

AU - Walsh, Christopher T.

AU - Calderone, Christopher T.

PY - 2008/9/3

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AB - Polyketide biosynthesis is typically directed by cis-acting catalytic domains. In the case of the Bacillus subtilis secondary metabolite dihydrobacillaene, the cis-acting domains are not sufficient to generate the saturated C14′-C15′ bond. In this communication, we identify PksE as a trans-acting enoyl reductase utilized in the biosynthesis of this portion of dihydrobacillaene. PksE is homologous to the enzymes predicted to serve as enoyl reductases in polyunsaturated fatty acid (PUFA) biosynthesis, and we confirmed this functional assignment in vitro. These results suggest a general enoyl reduction pathway in polyketide biosynthesis and a means by which PUFA-like biosynthetic machinery can modulate small-molecule function.

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Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis

Abstract

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