Article abstract
Nature Chemical Biology 4, 617 - 623 (2008)
Published online: 7 September 2008 | doi:10.1038/nchembio.113
Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases
Paul E O'Maille1, Arthur Malone1, Nikki Dellas1,2, B Andes Hess Jr3, Lidia Smentek3,4, Iseult Sheehan1, Bryan T Greenhagen5, Joe Chappell5, Gerard Manning6 & Joseph P Noel1
Abstract
Throughout molecular evolution, organisms create assorted chemicals in response to varying ecological niches. Catalytic landscapes underlie metabolic evolution, wherein mutational steps alter the biosynthetic properties of enzymes. Here we report the first systematic quantitative characterization of the catalytic landscape underlying the evolution of sesquiterpene chemical diversity. On the basis of our previous discovery of a set of nine naturally occurring amino acid substitutions that functionally interconverted orthologous sesquiterpene synthases from Nicotiana tabacum and Hyoscyamus muticus, we created a library of all possible residue combinations (29 = 512) in the N. tabacum enzyme. The product spectra of 418 active enzymes revealed a rugged landscape where several minimal combinations of the nine mutations encode convergent solutions to the interconversions of parental activities. Quantitative comparisons indicated context dependence for mutational effects—epistasis—in product specificity and promiscuity. These results provide a measure of the mutational accessibility of phenotypic variability in a diverging lineage of terpene synthases.
- Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Jack H. Skirball Center for Chemical Biology & Proteomics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
- Department of Chemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
- Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, Tennessee 37235, USA.
-
Institute of Physics, Nicolaus Copernicus University, Grudziadzka 5/7, 87-100 Toru
, Poland. - Department of Plant & Soil Sciences, Plant Biology Program, University of Kentucky, 105 Plant Science Building, 1405 Veterans Drive, Lexington, Kentucky 40546, USA.
- The Salk Institute for Biological Studies, Razavi Newman Center for Bioinformatics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Correspondence to: Joseph P Noel1 e-mail: noel@salk.edu
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