Broad substrate specificity of ketoreductases derived from modular polyketide synthases

Shilpa Bali; Helen M. O'Hare; Kira J. Weissman

doi:10.1002/cbic.200500430

Broad substrate specificity of ketoreductases derived from modular polyketide synthases

Shilpa Bali, Helen M. O'Hare, Kira J. Weissman

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

37 Scopus citations

Abstract

Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular polyketide synthases (PKSs) have been examined as potential catalysts for the enantioselective reduction of non-polyketide substrates. KR domains from two modular PKSs show significant activity toward alternative substrates, particularly those that incorporate cyclohexyl moieties. Through site-directed mutagenesis of the amino acid motifs previously implicated in stereocontrol by KRs, we have identified mutants with improved activity toward such compounds. These results suggest that PKS KRs could potentially be used as biotransformation catalysts for the production of chiral alcohols.

Original language	English
Pages (from-to)	478-484
Number of pages	7
Journal	ChemBioChem
Volume	7
Issue number	3
DOIs	https://doi.org/10.1002/cbic.200500430
State	Published - Mar 2006
Externally published	Yes

Keywords

Biosynthesis
Biotransformations
Broad specificity
Oxidoreductases
Polyketide synthase

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10.1002/cbic.200500430

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abstract = "Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular polyketide synthases (PKSs) have been examined as potential catalysts for the enantioselective reduction of non-polyketide substrates. KR domains from two modular PKSs show significant activity toward alternative substrates, particularly those that incorporate cyclohexyl moieties. Through site-directed mutagenesis of the amino acid motifs previously implicated in stereocontrol by KRs, we have identified mutants with improved activity toward such compounds. These results suggest that PKS KRs could potentially be used as biotransformation catalysts for the production of chiral alcohols.",

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AU - Bali, Shilpa

AU - O'Hare, Helen M.

AU - Weissman, Kira J.

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N2 - Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular polyketide synthases (PKSs) have been examined as potential catalysts for the enantioselective reduction of non-polyketide substrates. KR domains from two modular PKSs show significant activity toward alternative substrates, particularly those that incorporate cyclohexyl moieties. Through site-directed mutagenesis of the amino acid motifs previously implicated in stereocontrol by KRs, we have identified mutants with improved activity toward such compounds. These results suggest that PKS KRs could potentially be used as biotransformation catalysts for the production of chiral alcohols.

AB - Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular polyketide synthases (PKSs) have been examined as potential catalysts for the enantioselective reduction of non-polyketide substrates. KR domains from two modular PKSs show significant activity toward alternative substrates, particularly those that incorporate cyclohexyl moieties. Through site-directed mutagenesis of the amino acid motifs previously implicated in stereocontrol by KRs, we have identified mutants with improved activity toward such compounds. These results suggest that PKS KRs could potentially be used as biotransformation catalysts for the production of chiral alcohols.

KW - Biosynthesis

KW - Biotransformations

KW - Broad specificity

KW - Oxidoreductases

KW - Polyketide synthase

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M3 - Artículo

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SN - 1439-4227

VL - 7

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EP - 484

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ER -

Broad substrate specificity of ketoreductases derived from modular polyketide synthases

Abstract

Keywords

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