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Insights into the Role of Ketoreductases in the Biosynthesis of Partially Reduced Bacterial Aromatic Polyketides.


ABSTRACT: Partially reduced aromatic polyketides are bioactive secondary metabolites or intermediates in the biosynthesis of deoxygenated aromatics. For the antibiotic GTRI-02 (mensalone) in different Streptomyces spp., biosynthesis involving the reduction of a fully aromatized acetyltrihydroxynaphthalene by a naphthol reductase has been proposed and shown in vitro with a fungal enzyme. However, more recently, GTRI-02 has been identified as a product of the ActIII biosynthetic gene cluster from Streptomyces coelicolor A3(2), for which the reduction of a linear polyketide precursor by ActIII ketoreductase, prior to cyclization and aromatization, has been suggested. We have examined three different ketoreductases from bacterial producer strains of GTRI-02 for their ability to reduce mono-, bi-, and tricyclic aromatic substrates. The enzymes reduced 1- and 2-tetralone but not other aromatic substrates. This strongly suggests a reduction of a cyclized but not yet aromatic polyketide intermediate in the biosynthesis of GTRI-02. Implications of the results for the biosynthesis of other secondary polyketidic metabolites are discussed.

SUBMITTER: Husain SM 

PROVIDER: S-EPMC7154522 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Insights into the Role of Ketoreductases in the Biosynthesis of Partially Reduced Bacterial Aromatic Polyketides.

Husain Syed Masood SM   Präg Andreas A   Linnenbrink Anton A   Bechthold Andreas A   Müller Michael M  

Chembiochem : a European journal of chemical biology 20191209 6


Partially reduced aromatic polyketides are bioactive secondary metabolites or intermediates in the biosynthesis of deoxygenated aromatics. For the antibiotic GTRI-02 (mensalone) in different Streptomyces spp., biosynthesis involving the reduction of a fully aromatized acetyltrihydroxynaphthalene by a naphthol reductase has been proposed and shown in vitro with a fungal enzyme. However, more recently, GTRI-02 has been identified as a product of the ActIII biosynthetic gene cluster from Streptomyc  ...[more]

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