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October 26, 2015
Very Important Paper: Comparison of 10,11-Dehydrocurvularin Polyketide Synthases from Alternaria cinerariae and Aspergillus terreus Highlights Key Structural Motifs
Rachel V. K. Cochrane, Zhizeng Gao, Gareth R. Lambkin, Wei Xu, Jaclyn M. Winter, Sandra L. Marcus, Yi Tang, John C. Vederas*
Genome sequencing of two distantly related fungi, Aspergillus terreus and Alternaria cinerariae, which both produce the phytotoxic anticancer agent, 10,11-dehydrocurvularin, afforded a unique opportunity to compare different enzymes that construct the same macrocyclic lactone. In each organism, two polyketide synthases are required for multistep assembly of this metabolite. Although these large multifunctional proteins have ~75% sequence identity overall, Vederas (University of Alberta, Canada) and co-workers found significant differences on certain surfaces of the proteins and in regions that link domains within the enzymes. Interestingly, modeling studies revealed different active-site cavity geometries and other key structural motifs that are thought to be important for product formation.
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