Prenyltransferases as key enzymes in primary and secondary metabolism

Abstract

Attachment of isoprene units to various acceptors by prenylation plays an important role in primary and secondary metabolism of living organisms. Protein prenylation belongs to posttranslational modification and is involved in cellular regulation process. Prenylated secondary metabolites usually demonstrate promising biological and pharmacological activities. Prenyl transfer reactions catalyzed by prenyltransferases represent the key steps in the biosynthesis and contribute significantly to the structural and biological diversity of these compounds. In the last decade, remarkable progress has been achieved in the biochemical, molecular, and structural biological investigations of prenyltransferases, especially on those of the members of the dimethylallyltryptophan synthase (DMATS) superfamily. Until now, more than 40 of such soluble enzymes are identified and characterized biochemically. They catalyze usually regioselective and stereoselective prenylations of a series of aromatic substances including tryptophan, tryptophan-containing peptides, and other indole derivatives as well as tyrosine or even nitrogen-free substrates. Crystal structures of a number of prenyltransferases have been solved in the past 10 years and provide a solid basis for understanding the mechanism of prenyl transfer reactions.

PrenDB, a Substrate Prediction Database to Enable Biocatalytic Use of Prenyltransferases

“…A prenyl moiety can be attached by prenyltransferases via its C1 (regular prenylation) or C3 (reverse prenylation) to carbon, oxygen, or nitrogen atoms of an acceptor (Fig. 1, A and B) (7,8). Together with the observed regiospecific prenylations at different positions of an acceptor molecule, prenyltransferases contribute significantly to the structural and biological diversity of natural products (7).…”

“…1, A and B) (7,8). Together with the observed regiospecific prenylations at different positions of an acceptor molecule, prenyltransferases contribute significantly to the structural and biological diversity of natural products (7).…”

“…Compared with their non-prenylated precursors, these compounds usually demonstrate distinct and often improved biological and pharmacological activities, which makes them promising candidates for drug discovery and development (1, 2, 4 -6). These compounds could be considered hybrid molecules of prenyl moieties of different chain lengths (n⅐C 5 , where n is an integer number) and aromatic skeletons originating from various biosynthetic pathways (7,8). Prenyl transfer reactions (i.e.…”

“…Based on their amino acid sequences and biochemical and structural characteristics, prenyltransferases are categorized into different subgroups (7). In the last decade, significant progress has been achieved with the members of the dimethylallyltryptophan synthase (DMATS) 5 superfamily, and Ͼ40 enzymes of this group were identified and characterized by mining of fungal and bacterial genomes (7).…”

“…In the last decade, significant progress has been achieved with the members of the dimethylallyltryptophan synthase (DMATS) 5 superfamily, and Ͼ40 enzymes of this group were identified and characterized by mining of fungal and bacterial genomes (7). These enzymes catalyze transfer reactions of a prenyl moiety from prenyl diphosphate (e.g.…”