Combinatorial biosynthesis for drug development.
Combinatorial biosynthesis can refer to any strategy for the genetic engineering of natural product biosynthesis to obtain new molecules, including the use of genetics for medicinal chemistry. However, it also implies the possibility that large libraries of complex compounds might be produced to feed a modern high-throughput screening operation. This review focuses on the multi-modular enzymes that produce polyketides, nonribosomal peptides, and hybrid polyketide-peptide compounds, which are the enzymes that appear to be most amenable to truly combinatorial approaches. The recent establishment of a high-throughput strategy for testing the activity of many non-natural combinations of modules from these enzymes should help speed the advance of this technology.
Menzella
Hugo G
HG
Kosan Biosciences, Inc. 3832 Bay Center Place, Hayward, CA 94545, USA.
Reeves
Christopher D
CD
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015394:Molecular Structure; D010453:Peptide Synthases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*
D004364:Pharmaceutical Preparations; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase