A fungal ketoreductase domain that displays substrate-dependent stereospecificity
نویسندگان
چکیده
Iterative highly reducing polyketide synthases from filamentous fungi are the most complex and enigmatic type of polyketide synthase discovered to date. Here we uncover an unusual degree of programming by the hypothemycin highly reducing polyketide synthase, in which a single ketoreductase domain shows stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed for the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.
منابع مشابه
Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketide synthases.
Table 1 classifies the KR domains in the PKSs reviewed in [4] and the amphotericin PKS. Fig. 4 shows the ClustalW-generated alignments of A and B-type KR domains. A-type KRs are above the gap, B-type below. In fatty acid and polyketide biosynthesis, dehydration of a β-hydroxyacyl chain normally forms a trans double bond. Fig. 5 shows alignments of the 88-103 region and the 134-149 region in KR ...
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2014). Insights into the programmed ketoreduction of partially reducing polyketide synthases : stereo-and substrate-specificity of the ketoreductase domain. One of the hallmarks of iterative polyketide synthases (PKS) is the programming mechanism which is essential for the generation of structurally diverse polyketide products. In partially reducing iterative PKSs (PR-PKS), the programming mech...
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