Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis

Progress in sequence analysis of biosynthetic gene clusters encoding polyke tides and nonribosomal peptides and in the reconstitution of in vitro activ ities continues to reveal new insights into the growth of these natural pro ducts' acyl chains, which have been revealed as a series of elongating, cov alent, acyl enzyme intermediates on their multimodular scaffolds. Studies t hat focus on the three stages of natural product biosynthesis - initiation, elongation, and termination - have yielded crucial information on monomer substrate specificity, domain and module portability, and product release m echanisms, all of which are important not only for an understanding of this exquisite enzymatic machinery, but also for the rational construction of n ew, functional synthetases and synthases that are a goal of combinatorial b iosynthesis.