The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii

Maxim Itkin, Rachel Davidovich-Rikanati, Shahar Cohen, Vitaly Portnoy, Adi Doron-Faigenboim, Elad Oren, Shiri Freilich, Galil Tzuri, Nadine Baranes, Shmuel Shen, Marina Petreikov, Rotem Sertchook, Shifra Ben-Dor, Hugo Gottlieb, Alvaro Hernandez, David R. Nelson, Harry S. Paris, Yaakov Tadmor, Yosef Burger, Efraim LewinsohnNurit Katzir, Arthur Schaffer

Research output: Contribution to journalArticlepeer-review

Abstract

The consumption of sweeteners, natural as well as synthetic sugars, is implicated in an array of modern-day health problems. Therefore, natural nonsugar sweeteners are of increasing interest. We identify here the biosynthetic pathway of the sweet triterpenoid glycoside mogroside V, which has a sweetening strength of 250 times that of sucrose and is derived from mature fruit of luohanguo (Siraitia grosvenorii, monk fruit). A whole-genome sequencing of Siraitia, leading to a preliminary draft of the genome, was combined with an extensive transcriptomic analysis of developing fruit. A functional expression survey of nearly 200 candidate genes identified the members of the five enzyme families responsible for the synthesis of mogroside V: squalene epoxidases, triterpenoid synthases, epoxide hydrolases, cytochrome P450s, and UDP-glucosyltransferases. Protein modeling and docking studies corroborated the experimentally proven functional enzyme activities and indicated the order of the metabolic steps in the pathway. A comparison of the genomic organization and expression patterns of these Siraitia genes with the orthologs of other Cucurbitaceae implicates a strikingly coordinated expression of the pathway in the evolution of this speciesspecific and valuable metabolic pathway. The genomic organization of the pathway genes, syntenously preserved among the Cucurbitaceae, indicates, on the other hand, that gene clustering cannot account for this novel secondary metabolic pathway.

Original languageEnglish (US)
Pages (from-to)E7619-E7628
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number47
DOIs
StatePublished - Nov 22 2016

Keywords

  • Functional genomics
  • Metabolic pathway discovery
  • Mogrosides

ASJC Scopus subject areas

  • General

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