Identification and functional characterization of oxidosqualene cyclases from medicinal plant Hoodia gordonii

Authors: PARVEEN, IFFAT - University Of Mississippi; Wang, Mei; ZHAO, JIANPING - University Of Mississippi; ZHU, YINGJIE - Memorial Sloan Kettering; CHITTIBOYINA, AMAR - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi; Pan, Zhiqiang - Peter

Submitted to: Plants
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2024
Publication Date: 1/14/2024
Citation: Parveen, I., Wang, M., Zhao, J., Zhu, Y., Chittiboyina, A.G., Khan, I.A., Pan, Z. 2024. Identification and functional characterization of oxidosqualene cyclases from medicinal plant Hoodia gordonii. Plants. 13(2):231. https://doi.org/10.3390/plants13020231.
DOI: https://doi.org/10.3390/plants13020231

Interpretive Summary: Hoodia (Hoodia gordonii), a cactus-type plant, grows naturally in Botswana, South Africa and Namibia. Hoodia dietary supplements had been promoted as appetite suppressants for weight loss. One of the active ingredients in the hoodia extracts was identified as P57, a steroidal glycoside, responsible for the putative appetite-suppressant effect. The general structure of a steroidal glycoside consists of a steroid molecule, a triterpenoid or steroidal skeleton, attached to a sugar (glycoside). To identify the enzyme(s) responsible for the synthesis of the triterpenoid precursor, we cloned two genes from hoodia plants. Functional characterization of the enzymes encoded by these genes indicated that the enzymes possess the catalytic activities of synthesizing lupeol and cycloartenol. These are important triterpenoids of the sterol class and precursors of steroidal glycoside. This study provides an opportunity to elucidate the biosynthetic pathways for sterol and triterpenoid production, and thus the synthesis of steroidal glycosides in this particular species.

Technical Abstract: 2,3-oxidosqualene to varied triterpenoids and phytosterols. Hoodia gordonii (Asclepiadacecae), a native of the Kalahari deserts of South Africa, Namibia, and Botswana, is being sold as one of the prevalent herbal supplements for weight loss. The appetite suppressant properties are attributed to P57AS3, an oxypregnane steroidal glycoside. At the molecular level, the enzymes involved in the biosynthesis of triterpenes and phytosterols from H. gordonii have not been reported in the literature. In the present investigation, predicted transcripts potentially encoding oxidosqualene cyclases were first identified by mining publicly available H. gordonii RNA-seq data sets. Recombinant enzyme studies with two of the OSCs-like sequences led to the identification of one monofunctional OSC, designated HgOSC1 which encodes lupeol synthase, and HgOSC2, a multifunctional cycloartenol synthase forming cycloartenol and other products.