Structural basis for selectivity in a highly reducing type II polyketide synthase.
Nat Chem Biol
; 16(7): 776-782, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32367018
ABSTRACT
In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a ß-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Transportadora de Acilo
/
Proteínas de Escherichia coli
/
Sintasas Poliquetidas
/
Escherichia coli
/
Ácido Graso Sintasas
/
Policétidos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón