BBMB Research Seminars

Dr. Joe Noel
Salk Institute
“Quantitative Exploration of the Catalytic Landscape Separating Divergent Plant Sesquiterpene Synthases"
Abstract

1414 Molecular Biology Buidling
4:40 p.m.

Abstract:

Currently, no clearly discernable set of predictive relationships exists linking sequence variation and the complex chemical output of secondary metabolic enzymes based on phylogenetic analyses alone. Previously, we discovered a limited set of naturally occurring mutations capable of inter-converting distinct activities in a pair of phylogenetically-related plant sesquiterpene synthases. This discovery provided the basis for creating the enzyme lineages linking these evolutionarily related synthases. Notably, numerous mutants exhibit relaxed product specificity, consistent with suggestions that specific enzymatic activities evolve from promiscuous catalytic intermediates. Strikingly, we discovered several saltatory specificity switches arising from single mutations, depending on the mutant background. Collectively, these results demonstrate the rapid evolvability of chemical diversity in terpene synthases. Moreover, this work takes a first step towards quantitatively defining the interrelationship between sequence space and chemical complexity by comprehensively exploring the mutational landscape that underlies the divergent evolution of metabolic activities.