Antibiotic Assembly Line

Polyketides, a promising group of chemical compounds with antibacterial, immunosuppressant, antiparasitic and anticancer activity, are naturally synthesized in streptomycete bacteria by large, complex enzymes that function as molecular assembly lines of two-carbon building blocks. Theoretically a simple proposition, the rapid and systematic generation of new types of polyketide-synthesizing enzymes through genetic engineering has until now eluded researchers owing to the inherent complexities of manipulating large stretches of 'functional' DNA sequences from different streptomycete bacteria.

Now, by combining DNA sequences encoding subunits of a particular antibiotic-manufacturing enzyme complex from different microorganisms and expressing them in a single bacterium, Daniel Santi and colleagues were able to 'mix and match' chemical building blocks. These chemical building blocks, which are fused together to make polyketide antibiotics such as erythromycin and amphotericin, are freely combined by the hybrid enzyme complexes to make a diverse range of new compounds with potential antibiotic activity. The ability to rapidly generate these compounds may provide new leads for antibiotics to combat strains of bacteria resistant to current drugs.

Author Contact:

Daniel V. Santi (KOSAN Biosciences, Inc., Hayward, CA, USA)
E-mail: santi@kosan.com

Abstract available online.

(C) Nature Biotechnology.

Message posted by: Trevor M. D'Souza