Structure and mechanism of the 6-deoxyerythronolide B synthase.

Chaitan Khosla, Yinyan Tang, Alice Y Chen, Nathan A Schnarr, David E Cane

Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA. khosla@stanford.edu

Annual review of biochemistry 2007

filter terms:

6-Deoxyerythronolide B, the macrocyclic aglycone of the antibiotic erythromycin, is synthesized by a polyketide synthase (PKS) that has emerged as the prototypical modular megasynthase. A variety of molecular biological, protein chemical, and biosynthetic experiments over the past two decades have yielded insights into its mechanistic features. More recently, high-resolution structural images of portions of the 6-deoxyerythronolide B synthase have provided a platform for interpreting this wealth of biochemical data, while at the same time presenting a fundamentally new basis for the design of more detailed investigations into this remarkable enzyme. For example, the critical roles of domain-domain interactions and nonconserved linkers, as well as large interdomain movements in the structure and function of modular PKSs, have been highlighted. In turn, these insights point the way forward for more sophisticated and efficient biosynthetic engineering of complex polyketide natural products.

Citation

Chaitan Khosla, Yinyan Tang, Alice Y Chen, Nathan A Schnarr, David E Cane. Structure and mechanism of the 6-deoxyerythronolide B synthase. Annual review of biochemistry. 2007;76:195-221