Taxonomic distribution of proteins containing PKS_PP_betabranch domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing PKS_PP_betabranch domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

A conserved motif flags acyl carrier proteins for beta-branching in polyketidesynthesis.

Haines AS, Dong X, Song Z, Farmer R, Williams C, Hothersall J, Ploskon E, Wattana-amorn P, Stephens ER, Yamada E, Gurney R, Takebayashi Y, Masschelein J, Cox RJ, Lavigne R, Willis CL, Simpson TJ, Crosby J, Winn PJ, Thomas CM, Crump MP
Nat Chem Biol. 2013; 9: 685-92

Type I polyketide synthases often use programmed beta-branching, via enzymes of a'hydroxymethylglutaryl-CoA synthase (HCS) cassette', to incorporate various side chains at the second carbon from the terminal carboxylic acid of growingpolyketide backbones. We identified a strong sequence motif in acyl carrierproteins (ACPs) where beta-branching is known to occur. Substituting ACPsconfirmed a correlation of ACP type with beta-branching specificity. Althoughthese ACPs often occur in tandem, NMR analysis of tandem beta-branching ACPsindicated no ACP-ACP synergistic effects and revealed that the conserved sequencemotif forms an internal core rather than an exposed patch. Modeling andmutagenesis identified ACP helix III as a probable anchor point of the ACP-HCScomplex whose position is determined by the core. Mutating the core affects ACPfunctionality, whereas ACP-HCS interface substitutions modulate systemspecificity. Our method for predicting beta-carbon branching expands thepotential for engineering new polyketides and lays a basis for determiningspecificity rules.