Combinatorial biosynthesis of erythromycin and complex polyketides.
Modular polyketide synthases that produce many clinically important natural products such as erythromycins and lovastatins have been engineered in many ways to produce novel natural products. The structural variations have included alterations to the substituents on the macrolide ring, including the starter acid residue, using either semi-synthetic methodology or genetic engineering. It is now also possible to produce shorter polyketide chains that are released either as lactone rings (6-, 8-, 12- and 14-membered rings) or linear products. The strategies for engineering polyketide synthases to produce specific natural products are now well established. Several of the macrolides produced recently have been elaborated to produce novel antibiotics.
Staunton
J
J
Department of Chemistry, University of Cambridge, UK. js24@cam.ac.uk
D015195:Drug Design; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000737:chemistry; D005818:Genetic Engineering / Q000379:methods; D018942:Macrolides / Q000138:chemical synthesis*; D009097:Multienzyme Complexes
D018942:Macrolides; D009097:Multienzyme Complexes; D004917:Erythromycin