期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 30, 页码 E4407-E4414出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1605509113
关键词
terpenes; natural products; plant defense; cyclization; mutants
资金
- European Union Grant (TriForC) [KBBE-2013-7]
- Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant Understanding and Exploiting Plant and Microbial Metabolism [BB/J004561/1]
- John Innes Foundation
- Norwich Research Park studentship award
- BBSRC [BBS/E/J/000CA533, BBS/E/J/000CA446, BB/L014130/1, BB/K005952/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/J/000CA533, BB/L014130/1, BBS/E/J/00000614, BBS/E/J/000CA446, BB/K005952/1] Funding Source: researchfish
Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.
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