MENZELLA Hugo Gabriel
congresos y reuniones científicas
Invited speaker: Combinatorial biosynthesis by de novo design of modular polyketide synthesis genes
Santa Fe, NM, USA
Conferencia; Natural Products Discovery and Production Conference; 2006
Type I polyketide synthase (PKS) genes recapitulate nature’s commonly used strategy of modular biosynthesis. Modules of ~3 to ~6 kb serve to encode structures of 2-carbon units in a polyketide product. Genetic alteration or replacement of PKS modules can lead to “unnatural” natural products, but techniques to do so have been extremely slow. Here we describe a generic design of synthetic PKS genes where modules and domains are flanked by a repeated set of restriction sites, allowing facile cassette assembly and interchange. As a test of feasibility, we synthesized 14 modules from eight PKS clusters and associated them in 154 bimodular combinations that span over 1.5 million bp of novel PKS gene sequences. Remarkably, nearly half of the combinations made 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 to order.