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Thesis Defence: The Quest for New Enzymes Involved in the Biosynthetic Pathway of the Anticancer Drug Camptothecin from Camptotheca acuminata
November 16, 2023 at 10:00 am - 1:00 pm
Helena Hitomi Chubatsu Nunes, supervised by Dr. Thuy Dang, will defend their thesis titled “The Quest for New Enzymes Involved in the Biosynthetic Pathway of the Anticancer Drug Camptothecin from Camptotheca acuminata” in partial fulfillment of the requirements for the degree of Master of Science in Biochemistry and Molecular Biology.
An abstract for Helena Hitomi Chubatsu Nunes’ thesis is included below.
Defences are open to all members of the campus community as well as the general public. Registration is not required for in person defences.
ABSTRACT
Camptothecin (CPT) is a monoterpene indole alkaloid extracted from the Chinese native tree Camptotheca acuminata, commonly known as Happy Tree. Since its discovery in 1958, CPT has been derivatized to produce the widely used DNA Topoisomerase I inhibitors and anticancer drugs Topotecan and Irinotecan. The low natural abundance of camptothecin and complex chemical structure challenge synthetic routes and hinder green production strategies that attempt to obtain this essential pharmaceutical. Thefore, the elucidation of its biosynthetic pathway will pave the way for sustainable alternatives to access CPT’s medical properties. This thesis focused on the investigation of two biosynthetic steps: the formation of CPT’s main intermediate, strictosidinic acid, as well as the enzymatic rearrangement of the indole moiety in the intermediate strictosamide. Strictosidine synthases from C. acuminata were able to condense secologanin and tryptamine to form the ester-based compound strictosidine, challenging the putative CPT pathway currently based on carboxylic acid intermediates. Furthermore, C. acuminata dioxygenase was identified as able to convert strictosamide into putative oxidized forms. Overall, this thesis is a step forward in the understanding of CPT biosynthesis and sets the stage for future gene discovery opportunities to promote more a sustainable and economic production of CPT and clinically relevant derivatives.
