Affiliation: | 1. Centre of Biomedical Research, SGPGIMS Campus, Raebareli Road, Lucknow, 226014 Uttar Pradesh, India
These authors contributed equally to this work.;2. Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg, Germany
These authors contributed equally to this work.;3. Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany;4. Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg, Germany |
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. |