Ketoreduction in mycolactone biosynthesis: insight into substrate specificity and stereocontrol from studies of discrete ketoreductase domains in vitro.
Chembiochem
; 7(12): 1935-42, 2006 Dec.
Article
en En
| MEDLINE
| ID: mdl-17031885
Mycolactone, a polyketide toxin responsible for the extensive tissue destruction seen in Buruli ulcer, is assembled on a modular polyketide synthase (PKS). Despite operating on structurally different intermediates during synthesis, many of the ketoreductase (KR) domains of the mycolactone (MLS) PKS have identical sequences. This suggests that these enzymes might exhibit an unusually high level of substrate promiscuity. However, we show here that when recombinant mycolactone KR domains are tested with a range of surrogate substrates, their specificity closely matches that of KR domains derived from other PKS systems. In addition, our findings reinforce the role of substrate tethering for achieving stereochemical control in modular PKSs by affecting the delicate energetics of ketoreduction.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Toxinas Bacterianas
/
Sintasas Poliquetidas
/
Cetonas
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2006
Tipo del documento:
Article
Pais de publicación:
Alemania