Johnson, Colin
Colin is in the Chemistry Graduate Program, and joined the CMB Training Program in 2022.
Mentor: Dr. Yi Tang
Cannabinoids are a large class of bioactive natural products derived from the Cannabis sativa plant that modulate the CB1 and CB2 cannabinoid receptors of the human endocannabinoid system. While over 100 different cannabinoids have been identified, the two most studied compounds also happen to be the most abundant: Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Many of the remaining minor cannabinoids demonstrate unique properties and mechanisms apart from those of THC and CBD but remain largely underexplored due to limitations including (1) prohibitively low abundance in planta; (2) significant land and water requirements; and (3) complicated inconsistent mixture of products. Thus, a more sustainable and reliable source of cannabinoids is critical not only to meet consumer demand, but also to access sufficient quantities of rare and novel cannabinoid analogues for therapeutic evaluation.
Microbial fermentation platforms are a potentially disruptive technology to address these limitations. Recently, the Tang Lab identified a new fungal pathway capable of producing high titers of olivetolic acid, a key cannabinoid precursor. Furthermore, the Tang Lab recently acquired an invaluable fungal strain collection with hundreds of unsequenced and unexplored biosynthetic potential. These not only provide me a unique opportunity to identify IP-free pathways to classic phytocannabinoids, but also to discover alternative biosynthetic routes to downstream compounds. In addition to fully reconstituting biosynthetic pathways, I intend to leverage the Tang Lab’s expertise in bioinformatic mining to identify interesting targets in sequenced genomes, followed by genome mining and enzyme characterization. Identifying enzymes that can be used to selectively modify the cannabinoid scaffold via biocatalysis is an area of focus I find particularly compelling. In combining genome mining and synthetic biology approaches, I aim to identify enzyme targets that can be integrated into the Tang Lab’s combinatorial biosynthesis platform to generate novel cannabinoid analogues with enhanced or differing bioactivities. My future goals are to meaningfully contribute to the research of bioactive natural products, their unique biosynthetic machinery, and their biomedical and biotechnological applications to improve human health.
