Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants

  • Nat Commun. 2019 Jul 19;10(1):3206. doi: 10.1038/s41467-019-11286-7.
Bastien Christ  1  2 ,  Chengchao Xu  1 ,  Menglong Xu  1 ,  Fu-Shuang Li  1 ,  Naoki Wada  3 ,  Andrew J Mitchell  1 ,  Xiu-Lin Han  4 ,  Meng-Liang Wen  4 ,  Makoto Fujita  3  5 ,  Jing-Ke Weng  6  7
Affiliations
  • 1. Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.
  • 2. Agroscope, Route des Eterpys 18, 1964, Conthey, Switzerland.
  • 3. Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
  • 4. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Institute of Microbiology, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.
  • 5. Division of Advanced Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan.
  • 6. Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA. [email protected].
  • 7. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. [email protected].
PMID: 31324795 DOI: 10.1038/s41467-019-11286-7
Abstract

Diosgenin is a spiroketal steroidal natural product extracted from Plants and used as the single most important precursor for the world steroid hormone industry. The sporadic occurrences of diosgenin in distantly related Plants imply possible independent biosynthetic origins. The characteristic 5,6-spiroketal moiety in diosgenin is reminiscent of the spiroketal moiety present in anthelmintic avermectins isolated from actinomycete bacteria. How Plants gained the ability to biosynthesize spiroketal natural products is unknown. Here, we report the diosgenin-biosynthetic pathways in himalayan paris (Paris polyphylla), a monocot medicinal plant with hemostatic and Antibacterial properties, and fenugreek (Trigonella foenum-graecum), an eudicot culinary herb plant commonly used as a galactagogue. Both Plants have independently recruited pairs of cytochromes P450 that catalyze oxidative 5,6-spiroketalization of Cholesterol to produce diosgenin, with evolutionary progenitors traced to conserved Phytohormone metabolism. This study paves the way for engineering the production of diosgenin and derived analogs in heterologous hosts.

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