Plant steroidal specialized metabolism
Sterols are isoprenoid-derived molecules essential for normal growth and development of all eukaryotes. Sterols are also the precursors for many secondary or specialized metabolites. Steroidal molecules have become an integral part of human health (steroid hormones; e.g. progesterone, estrogen), nutrition (e.g. vitamin D supplements, dietary supplements such as Tribulus extracts) and medicine [steroidal drugs for treatments ranging from mild inflammation, allergies to chronic illness and diseases (e.g. cancer)]. During the COVID-19 outbreak, two steroidal molecules methylprednisolone and dexamethansone, approved by the World Health Organization, were used worldwide in COVID-19 treatment therapy. Compared to animals and fungi, which each produce one major sterol, plants produce a spectacular range of sterol molecules, making them a promising source of ‘high-value’ steroidal compounds. To meet the increasing demands of high-value steroidal compounds, synthetic biology and metabolic engineering approaches are required for high scale production of these compounds. Unfortunately, our knowledge about biosynthesis of many steroidal specialized metabolites (e.g. cardenolides) is extremely limited, therefore constraining state-of-the-art synthetic biology applications that can harness this class of metabolites. Moreover, our access to certain high value steroids (e.g. pro-vitamin D3 and vitamin D3) in sustainable plant production systems remains restricted, as these compounds are produced in small amounts in only a few plant species. With the capacity to apply new technological advances in sequencing, bioinformatics and metabolomics across multiple plant species, coupled with optimized heterologous production systems, we are now poised to solve the outstanding question of steroidal specialized metabolism that has eluded researchers for decades.
Our research aims to tackle two key challenges required to harness plant steroidal metabolism: 1) the discovery of downstream enzymes that convert sterols into high-value specialized metabolites, and 2) metabolic engineering for sustainable production of these compounds in plants.