Enzymatic studies on aromatic prenyltransferases

Abstract

Aromatic prenyltransferases (PTases), including ABBA-type and dimethylallyl tryptophan synthase (DMATS)-type enzymes from bacteria and fungi, play important role for diversification of the natural products and improvement of the biological activities. For a decade, the characterization of enzymes and enzymatic synthesis of prenylated compounds by using ABBA-type and DMATS-type PTases have been demonstrated. Here, I introduce several examples of the studies on chemoenzymatic synthesis of unnatural prenylated compounds and the enzyme engineering of ABBA-type and DMATS-type PTases.

Keywords: Aromatic prenyltransferase; Biosynthesis; Enzyme engineering; Prenylated compounds.

Fig. 1

The overall structures of ABBA-type and DMATS-type PTases. The crystal structure and reaction of a NphB and b FgaPT2

Fig. 2

Examples of the prenylation substrates of ABBA-type and DMATS-type PTases. The highlighted atoms are the major prenylation points. The prenylation positions of non-highlighted compounds are not determined

Fig. 3

The substrate specificity of a TleC, MpnD, and b AtaPT toward prenyl donors

Fig. 4

Structures of the synthetic unnatural prenyl donors tested for FgaPT2 and SirD. The substrates highlighted in purple, red, and blue are tested for the both of FgaPT2 and SirD, only SirD, and only FgaPT2, respectively. The substrates enclosed in red and blue frames are accepted by SirD and FgaPT2, respectively

Fig. 5

The enzyme reactions of engineered ABBA-type and DMATS-type PTases. The enzyme reaction of a the FgaPT2 and its K174F/K244X mutants, b the FtmPT1 and its Y205X mutants, c the TleC W97Y/A173M and W97Y/F170W/A173M mutants, and d FgaPT2 and its M328X mutants