1. Heterologous Biosynthesis of Tetrahydroxanthone Dimers: Determination of Key Factors for Selective or Divergent Synthesis.
- Author
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Wei X, Chen X, Chen L, Yan D, Wang WG, and Matsuda Y
- Subjects
- Aspergillus oryzae genetics, Biosynthetic Pathways, Molecular Structure, Transformation, Genetic, Aspergillus oryzae enzymology, Genes, Fungal, Multigene Family, Xanthones metabolism
- Abstract
Tetrahydroxanthone dimers are fungal products, among which secalonic acid D ( 1 ) is one of the most studied compounds because of its potent biological activity. Because the biosynthetic gene cluster of 1 has been previously identified, we sought to heterologously produce 1 in Aspergillus oryzae by expressing the relevant biosynthetic genes. However, our initial attempt of the total biosynthesis of 1 failed; instead, it produced four isomers of 1 due to the activity of an endogenous enzyme of A. oryzae . Subsequent overexpression of the Baeyer-Villiger monooxygenase, AacuH, which competes with the endogenous enzyme, altered the product profile and successfully generated 1 . Characterization of the key biosynthetic enzymes revealed the surprising substrate promiscuity of the dimerizing enzyme, AacuE, and indicated that efficient synthesis of 1 requires highly selective preparation of the tetrahydroxanthone monomer, which is apparently controlled by AacuH. This study facilitates engineered biosynthesis of tetrahydroxanthone dimers both in a selective and divergent manner.
- Published
- 2021
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