Enzymatic studies on aromatic prenyltransferases
- PDF / 2,850,916 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 107 Downloads / 201 Views
REVIEW
Enzymatic studies on aromatic prenyltransferases Takahiro Mori1 Received: 15 January 2020 / Accepted: 5 March 2020 © The Japanese Society of Pharmacognosy 2020
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 ABBAtype 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 Biosynthesis · Enzyme engineering · Aromatic prenyltransferase · Prenylated compounds
Introduction The prenylated indole alkaloids and prenylated aromatic compounds isolated from plants and microorganisms show broad structural diversity and various biological activities [1–6]. The prenylation may increase the lipophilicity and/ or binding ability to target protein that directly influences the biological activity [7, 8]. The prenylation to aromatic compounds is catalyzed by the several enzyme groups of prenyltransferases (PTases), including membrane-embedded UbiA-type, bacterial and fungal ABBA-type, and fungal dimethylallyl tryptophan synthase (DMATS)-type PTases [9–20]. UbiA-type PTases possess a conserved (N/D)DXXD motif for binding of M g2+ ion and diphosphate that is also conserved in the isoprenyl diphosphate synthases [9, 10]. The enzymes in this group are observed in the ubiquinone and menaquinone biosynthesis [10], membrane lipids biosynthesis in archaea [21], in the biosynthesis of prenylated aromatic secondary metabolites in plants [1], and fungal meroterpenoid biosynthesis [22]. On the other hand, ABBAtype and DMATS-type PTases from microorganisms are soluble proteins and do not contain diphosphate and metal ion binding motif [11–18, 20]. The soluble aromatic PTases
* Takahiro Mori [email protected]‑tokyo.ac.jp 1
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7‑3‑1 Hongo, Bunkyo‑ku, Tokyo 113‑0033, Japan
are involved in the biosynthesis of secondary metabolites in bacteria and fungi. In the present review, several examples of the recent studies on chemoenzymatic synthesis and the enzyme engineering of soluble ABBA-type and DMATS-type PTases to generate unnatural prenylated aromatic compounds are provided.
Soluble aromatic PTases ABBA-type and DMATS-type aromatic PTases catalyze prenylation of dimethylallyl diphosphate (DMAPP) and/ or geranyl diphosphate (GPP) to aromatic compounds in bacteria and fungi. The ABBA-type PTases are identified from both of bacteria and fungi, and the CloQ from Streptomyces roseochromogenes var. oscitans is a first characterized ABBA-type of PTases in 2003, which is involved in the biosynthesis of clorobiocin [23]. Different from membranebound UbiA-type PTases, these enzyme reactions, except
Data Loading...
