Ta. Keating et Ct. Walsh, Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis, CURR OP C B, 3(5), 1999, pp. 598-606
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.