Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

Abstract

The cytochrome P450 monooxygenase (CYP) superfamily comprises hemethiolate enzymes that perform remarkable regio- and stereospecific oxidative chemistry. As such, CYPs are key agents for the structural and functional tailoring of triterpenoids, one of the largest classes of plant natural products with widespread applications in pharmaceuticals, food, cosmetics, and agricultural industries. In this review, we provide a full overview of 149 functionally characterised CYPs involved in the biosynthesis of triterpenoids and steroids in primary as well as in specialised metabolism. We describe the phylogenetic distribution of triterpenoid- and steroid-modifying CYPs across the plant CYPome, present a structure-based summary of their reactions, and highlight recent examples of particular interest to the field. Our review therefore provides a comprehensive up-to-date picture of CYPs involved in the biosynthesis of triterpenoids and steroids in plants as a starting point for future research.

Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree

“…This subgroup includes several other enzymes that are known to glycosylate triterpenes from both monocots and dicots (21). In summary, CSLM1/2, together with the three UGT enzymes characterized here, collectively enable the conversion of QA (5) to either QA-TriX (8) or QA-TriR (9) (Fig. 3C).…”

“…We next considered candidates for oxidation of β-amyrin ( 2 ). Most known triterpene oxidases are members of the cytochrome P450 monooxygenase (CYP) superfamily ( 8 ). Of these, the CYP716 family is commonly associated with triterpene biosynthesis and includes enzymes known to perform C-28 and C-16α oxidation ( 8 , 15 ).…”

“…Most known triterpene oxidases are members of the cytochrome P450 monooxygenase (CYP) superfamily ( 8 ). Of these, the CYP716 family is commonly associated with triterpene biosynthesis and includes enzymes known to perform C-28 and C-16α oxidation ( 8 , 15 ). A BLAST search of the 1KP Q. saponaria transcriptome dataset was performed using a known C-28 oxidase from Medicago truncatula (CYP716A12; GenBank accession no.…”

“…This issue is further exacerbated by variations in saponin content and composition between individual trees caused by environmental and genetic factors (4)(5)(6). Although a number of saponin biosynthetic enzymes have been characterized in recent years from taxonomically diverse plant species [e.g., (7)(8)(9)(10)], much remains to be learned about the enzymes that generate the enormous structural diversity of saponins. Indeed, QS-21 has a total of seven different types of glycosidic moieties, including unusual sugars such as D-fucose, D-apiose, and L-arabinofuranose, for which the cognate enzymes are not yet known.…”

“…)] compared with the C-3 xylose version [QA-TriX(8)] (data S4). We therefore opted to generate and purify the putative C-28 glycosides on the basis of the QA-TriR (9) scaffold.…”