Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases

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. We report the first systematic quantitative characterization of a catalytic landscape underlying the evolution of sesquiterpene chemical diversity. Based on our previous discovery of a set of 9 naturally occurring amino acid substitutions that functionally inter-converted orthologous sesquiterpene synthases from Nicotiana tabaccum and Hyoscyamus muticus, we created a library of all possible residue combinations (29 = 512) in the N. tabaccum parent. The product spectra of 418 active enzymes to reveal a rugged landscape where several minimal combinations of the 9 mutations encode convergent solutions to the inter-conversions of parental activities. Quantitative comparisons indicate context dependence for mutational effects - epistasis - in product specificity and promiscuity. These results provide a measure of the mutational accessibility of phenotypic variability among a diverging lineage of terpene synthases.

• Publication year

  2008

• Venue

  Nature Chemical Biology

• Publication date

  2008-09-07

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1038/nchembio.113PMID 18776889PMCID 2664519
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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