Enantioselective enzymes by computational design and in silico screening.
Angew Chem Int Ed Engl
; 54(12): 3726-30, 2015 Mar 16.
Article
en En
| MEDLINE
| ID: mdl-25651000
ABSTRACT
Computational enzyme design holds great promise for providing new biocatalysts for synthetic chemistry. A strategy to design small mutant libraries of complementary enantioselective epoxide hydrolase variants for the production of highly enantioenriched (S,S)-diols and (R,R)-diols is developed. Key features of this strategy (CASCO, catalytic selectivity by computational design) are the design of mutations that favor binding of the substrate in a predefined orientation, the introduction of steric hindrance to prevent unwanted substrate binding modes, and ranking of designs by high-throughput molecular dynamics simulations. Using this strategy we obtained highly stereoselective mutants of limonene epoxide hydrolase after experimental screening of only 37 variants. The results indicate that computational methods can replace a substantial amount of laboratory work when developing enantioselective enzymes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Epóxido Hidrolasas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2015
Tipo del documento:
Article