P126: Cluster analysis of microbial aromatic prenyltransferases

Aromatic prenyltransferases attach an isoprenoid moiety to an aromatic acceptor molecule. In the biosynthesis of ubiquinones, menaquinones and plastoquinones, aromatic prenylation reactions are catalyzed by membrane-bound prenyltransferases which have conserved (N/D)DxxD motifs for the binding of the isoprenoid substrates in form of Mg²⁺ complexes. In contrast, the aromatic prenyltransferases involved in the biosynthesis of many microbial secondary metabolites are soluble enzymes without (N/D)DxxD motifs. These enzymes include CloQ of clorobiocin biosynthesis and NphB of naphterpin biosynthesis in Streptomyces strains, as well as dimethylallyl tryptophan synthases (DMATS) and other indole prenyltransferases in fungi and bacteria. PSI-BLAST searches reveal 18 entries with sequence similarity to CloQ and NphB in the database, and more than 100 entries with similarity to DMATS. The crystal structures of NphB and DMATS show a novel protein fold, the PT barrel, and structure predictions suggest that also the above-mentioned enzymes with similarity to NphB and DMATS exhibit this fold. For enzymes characterised by the PT barrel fold, the name ABBA prenyltransferases has been suggested, referring to their αββα structural motif.

Within the investigated proteins, the prenyltransferases of the CloQ/NphB-group form a single cluster, comprising both bacterial and fungal enzymes. In contrast, the indole prenyltransferases from fungi (e.g. DMATS) and from bacteria (e.g. LtxC) form two distinct but homologous groups. PSI-BLAST searches reveal no sequence similarity between the CloQ/NphB group and the DMATS/LtxC group, but HHpred, a sensitive method based on the comparison of profile hidden Markov models, finds evidence for a distant evolutionary relationship between these two groups.