John Papp
Research Mentor(s): Filipa Barroso Pereira
Mentor Department: Life Sciences Institute, University of Michigan
Authors: John Papp, Christina McBride, Chloe Warrell, Filipa Pereira
Session: Session 2 (10:00am – 10:50am)
Presentation Type: Poster 100
Abstract
Since the discovery of penicillin, microorganisms have been paramount in the production of natural products that have revolutionized medicine and pharmacology, vastly improving our quality of life. For this study, we turned our attention to the production of two compounds of interest: premarineosin A, a promising antimalarial drug, and marineosin A, which has the potential to be used as an anti-cancer drug. Previously, premarineosin A was identified as a precursor metabolite in the marineosin production pathway in Streptomyces sp. CNQ617, but the very low production titers impaired further studies. We have identified the biosynthetic gene cluster for premarineosin A in Streptomyces eitanensis, and enhanced its production through media optimization and strain engineering approaches. Unlike the biosynthetic gene cluster encoded in Streptomyces sp. CNQ617, the pathway in S. eitanensis lacks MarA, the enzyme required for the conversion of premarineosin A to marineosin A. In this work, we aimed to engineer S. eitanensis for the production of marineosin A. To do so, we integrated marA from Streptomyces sp. CNQ617 into S. eitanensis genome to convert premarineosin into marineosin A. To further enhance production titers, we sought to design the first genome-scale metabolic model (GEM) of S. eitanensis to elucidate the native metabolic pathways that may limit compound production. Genetic modification guided by modeling approaches will be implemented in S. eitanensis to optimize the production of the two target compounds. This increased production will allow for the sustainable production of premarineosin A and marineosin A, enabling further medicinal chemistry studies.
