A conserved motif flags acyl carrier proteins for ß-branching in polyketide synthesis.
Nat Chem Biol
; 9(11): 685-692, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24056399
ABSTRACT
Type I polyketide synthases often use programmed ß-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 growing polyketide backbones. We identified a strong sequence motif in acyl carrier proteins (ACPs) where ß-branching is known to occur. Substituting ACPs confirmed a correlation of ACP type with ß-branching specificity. Although these ACPs often occur in tandem, NMR analysis of tandem ß-branching ACPs indicated no ACP-ACP synergistic effects and revealed that the conserved sequence motif forms an internal core rather than an exposed patch. Modeling and mutagenesis identified ACP helix III as a probable anchor point of the ACP-HCS complex whose position is determined by the core. Mutating the core affects ACP functionality, whereas ACP-HCS interface substitutions modulate system specificity. Our method for predicting ß-carbon branching expands the potential for engineering new polyketides and lays a basis for determining specificity rules.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína de Transporte de Acila
/
Sequência Conservada
/
Policetídeos
/
Hidroximetilglutaril-CoA Sintase
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article