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.
Highlights
Reduced aromatic polyketides are bioactive secondary metabolites or intermediates in the biosynthesis of deoxygenated aromatics
Often characterized by the presence of polycyclic structures, represent a class of widely distributed secondary metabolites.[1,2,3]. Many of these polyketides are used as drugs or exhibit other fascinating biological activities.[4]. Their biosynthesis is often executed by type II nonreducing polyketide synthases (NR-PKSs) in bacteria and iterative type I
Supporting information and the ORCID identification numbers for the authors of this article can be found under https://doi.org/10.1002/ cbic.201900357: sequence alignment, cloning, and expression of ketoreductases, synthesis of substrates, including purification and analytical data, and enzymatic reductions
Summary
Reduced aromatic polyketides are bioactive secondary metabolites or intermediates in the biosynthesis of deoxygenated aromatics. Often characterized by the presence of polycyclic structures, represent a class of widely distributed secondary metabolites.[1,2,3] Many of these polyketides are used as drugs or exhibit other fascinating biological activities.[4] Their biosynthesis is often executed by type II nonreducing polyketide synthases (NR-PKSs) in bacteria and iterative type I Müller Institut für Pharmazeutische Wissenschaften Albert-Ludwigs-Universität Freiburg Albertstrasse 25, 79104
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