Enediyne natural products: biosynthesis and prospect towards engineering novel antitumor agents.
This review gives a brief account on the current status of enediyne biosynthesis and the prospective of applying combinatorial biosynthesis methods to the enediyne system for novel analog production. Methods for cloning enediyne biosynthetic gene clusters are first reviewed. A unified paradigm for enediyne biosynthesis, characterized with (a) the enediyne PKS, (b) the enediyne PKS accessory enzymes, and (c) tailoring enzymes, is then presented. Strategies and tools for novel enediyne analog production by combinatorial biosynthesis are finally discussed. The results set the stage to decipher the molecular mechanism for enediyne biosynthesis and lay the foundation to engineer novel enediynes by combinatorial biosynthesis for future endeavors.
Shen
Ben
B
Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA. bshen@pharmacy.wisc.edu
Liu
Wen
W
Nonaka
Koichi
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000096:biosynthesis* / Q000737:chemistry; D003001:Cloning, Molecular; D020650:Combinatorial Chemistry Techniques; D005818:Genetic Engineering; D015335:Molecular Probes; D005810:Multigene Family
D000970:Antineoplastic Agents; D001688:Biological Products; D015335:Molecular Probes