Increasing structural diversity by prenylation-based modifications
Huomiao Ran, Pharmazeutische Biologie, Li, Shu-Ming (Prof. Dr.)
2020
Fungi have the ability to generate tremendously complex and diverse natural products. Fungal secondary metabolites are highly relevant in mankind's daily life by playing an important role in medicine, agriculture and manufacturing industries. Since the discovery of antibiotics in the first half of the last century, an enormous variety of natural products has been discovered in different fungi. With the advent of the genomics revolution, scientists have realized that the remarkable chemical
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... of fungal secondary metabolites has resulted from the diversification of biosynthetic gene clusters (BGC). Enzymes as efficient catalysts are the bridge between these biosynthetic genes and the resulting small molecules. The initial chemical scaffolds are assembled by backbone enzyme(s) and undergo decorations catalysed by a set of tailoring enzymes to mature the products. Prenyltransferases are one representative family of these tailoring enzymes. "Aromatic" prenyltransferases accept a broad spectrum of substrates including, but no limited to, indole derivatives, benzene carbaldehydes and naphthalenes. Prenylated metabolites can be further modified by enzymatic or nonenzymatic reactions to facilitate the functional group density. Thus, understanding the complexity and diversity of natural product scaffolds requires investigation of whole biosynthetic assembly lines in vivo as well as the participating enzymes and their mechanisms. There are substantial studies demonstrating the diversification of enzymatic post-modifications on prenyl moieties. For example, the nonheme FeII/2-oxoglutarate (2-OG)-dependent oxygenase FtmOx1 from Aspergillus fumigatus is involved in the biosynthesis of fumitremorgin-type mycotoxins and catalyses an endoperoxide formation by insertion of an oxygen molecule into two prenyl moieties. Following this work, we cloned and overexpressed its homologous gene NFIA_045530 from Neosartorya fischeri. The recombinant protein EAW25734 encoded by NFIA_045530 was purified to apparent homogeneity and incubate [...]
doi:10.17192/z2020.0492
fatcat:qlydzbtcgjaklgfq747hq3jmzi