INVESTIGADORES
MENZELLA Hugo Gabriel
artículos
Título:
Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes
Autor/es:
MENZELLA H.G.; REID R.; CARNEY J.; CHANDRAN S; REISINGER S.; PATEL K.; HOPWOOD D.; SANTI D.
Revista:
NATURE BIOTECHNOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2005 vol. 23 p. 1171 - 1176
ISSN:
1087-0156
Resumen:
Type I polyketide synthase (PKS) genes consist of modules approximately
3-6 kb long, which encode the structures of 2-carbon units in polyketide
products. Alteration or replacement of individual PKS modules can lead
to the biosynthesis of 'unnatural' natural products but existing
techniques for this are time consuming. Here we describe a generic
approach to the design of synthetic PKS genes where facile cassette
assembly and interchange of modules and domains are facilitated by a
repeated set of flanking restriction sites. To test the feasibility of
this approach, we synthesized 14 modules from eight PKS clusters and
associated them in 154 bimodular combinations spanning over 1.5-million
bp of novel PKS gene sequences. Nearly half the combinations
successfully mediated the biosynthesis of a polyketide in Escherichia
coli, and all individual modules participated in productive bimodular
combinations. This work provides a truly combinatorial approach for the
production of polyketides.