Dimethylallyltryptophan synthase CymD

UniProtKB accession:  A8M6W6

Grouped By:  Matching UniProtKB accession

UniProtKB description:  Dimethylallyltryptophan synthase; part of the gene cluster that mediates the biosynthesis of cyclic heptapeptides, known as cyclomarins and also of cyclic dipeptides, called cyclomarazines, which have both antimicrobial and cytotoxic effects (PubMed:18331040, PubMed:20055491). Catalyzes the reverse N-prenylation of monomeric L-tryptophan with dimethylallyl diphosphate (DMAPP) to form N-(1,1-dimethylallyl)-tryptophan (r-N-DMAT) (PubMed:18331040, PubMed:20055491, PubMed:22935004, PubMed:31251043). The formation of r-N-DMAT appears to proceed via the deprotonation of the indole nitrogen of tryptophan, which facilitates a nucleophilic attack on the carbocation that is forming on the dimethylallyl group as the diphosphate dissociates (PubMed:22935004). The N-(1,1-dimethylallyl)-tryptophan produced by CymD is combined with a range of standard and nonproteinogenic amino acid substrates to synthesize the peptides, a process that is probably catalyzed by the non-canonical nonribosomal peptide synthetase (NRPS), CymA (PubMed:18331040, PubMed:20055491). Other proteins in the cluster catalyze further modifications of the peptides including CymV which catalyzes the oxidation of olefinic cyclomarins and cyclomarazines to their respective epoxide derivatives (PubMed:18331040). Utilizes only DMAPP as the prenyl donor and has no requirement for divalent cations (PubMed:20055491).