The Promiscuous Flavin-Dependent Monooxygenase PboD from Increases the Structural Diversity of Hydroxylated Pyrroloindoline Diketopiperazines.

The potential of natural products as pharmaceutical and agricultural agents is based on their large structural diversity, resulting in part from modifications of the backbone structure by tailoring enzymes during biosynthesis. Flavin-dependent monooxygenases (FMOs), as one such group of enzymes, play an important role in the biosynthesis of diverse natural products, including cyclodipeptide (CDP) derivatives. The FMO PboD was shown to catalyze C-3 hydroxylation at the indole ring of -l-Trp-l-Leu in the biosynthesis of protubonines, accompanied by pyrrolidine ring formation.

Biosynthesis of -Terphenyls in Implies Enzymatic Reductive Dehydration and Spontaneous Dibenzofuran Formation.

-Terphenyls contain a central benzene ring substituted with two phenyl residues at its positions. Heterologous expression of a biosynthetic gene cluster from led to the formation of four new -terphenyl derivatives. Gene deletion experiments proved the formation and reductive dehydration of the terphenylquinone atromentin, followed by O-methylation and prenylation.

A Flavin-Dependent Oxygenase Catalyzes Hydroxylation and Simultaneous Pyrrolidine Ring Formation in Protubonine Biosynthesis in .

The hydroxylated and diacetylated -l-Trp-l-Leu derivative (-)-protubonine B was isolated from a culture of 3.3904. Genome mining led to the identification of a putative biosynthetic gene cluster coding for a bimodular nonribosomal peptide synthetase, a flavin-dependent monooxygenase, and two acetyltransferases.