The Enzymology of Combinatorial Biosynthesis
- 1 January 2003
- journal article
- review article
- Published by Taylor & Francis in Critical Reviews in Biotechnology
- Vol. 23 (2) , 95-147
- https://doi.org/10.1080/713609311
Abstract
Combinatorial biosynthesis involves the genetic manipulation of natural product biosynthetic enzymes to produce potential new drug candidates that would otherwise be difficult to obtain. In either a theoretical or practical sense, the number of combinations possible from different types of natural product pathways ranges widely. Enzymes that have been the most amenable to this technology synthesize the polyketides, nonribosomal peptides, and hybrids of the two. The number of polyketide or peptide natural products theoretically possible is huge, but considerable work remains before these large numbers can be realized. Nevertheless, many analogs have been created by this technology, providing useful structure-activity relationship data and leading to a few compounds that may reach the clinic in the next few years. In this review the focus is on recent advances in our understanding of how different enzymes for natural product biosynthesis can be used successfully in this technologyKeywords
This publication has 99 references indexed in Scilit:
- A Method for Prediction of the Locations of Linker Regions within Large Multifunctional Proteins, and Application to a Type I Polyketide SynthaseJournal of Molecular Biology, 2002
- Evidence for a Monomeric Structure of Nonribosomal Peptide SynthetasesChemistry & Biology, 2002
- The barbamide biosynthetic gene cluster: a novel marine cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl starter unitGene, 2002
- The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: characterization of a 20-kb DNA region and generation of hybrid structuresMolecular Genetics and Genomics, 2001
- Multiple hybrid polyketide synthase/non-ribosomal peptide synthetase gene clusters in the myxobacterium Stigmatella aurantiacaGene, 2001
- The X‐ray crystal structure of β‐ketoacyl [acyl carrier protein] synthase IFEBS Letters, 1999
- Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthaseChemistry & Biology, 1999
- The first gene in the biosynthesis of the polyketide antibiotic TA Of Myxococcus xanthus codes for a unique PKS module coupled to a peptide synthetaseJournal of Molecular Biology, 1999
- Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthaseGene, 1996
- Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl‐CoA:acyl carrier protein transacylase domains in modular polyketide synthasesFEBS Letters, 1995