Generation of multiple bioactive macrolides by hybrid modular polyketide synthases in Streptomyces venezuelae.
Chem Biol
; 9(2): 203-14, 2002 Feb.
Article
em En
| MEDLINE
| ID: mdl-11880035
ABSTRACT
The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase, leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Streptomyces
/
Antibacterianos
/
Complexos Multienzimáticos
País/Região como assunto:
America do sul
/
Venezuela
Idioma:
En
Revista:
Chem Biol
Assunto da revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos