Project Grant R21AI202225

The National Institute of Allergy and Infectious Diseases awarded the Regents of the University of Michigan $234,000 on August 14, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop sustainable production and derivatization of premarineosin A, a potent antimalarial compound.

The project establishes premarineosin A as a next-generation antimalarial agent by developing metabolic engineering strategies to achieve sustainable production of the compound and generating a library of premarineosin derivatives with enhanced antimalarial activity and selectivity. Premarineosin A, derived from engineered Streptomyces eitanensis, demonstrates superior efficacy and reduced cytotoxicity compared to existing antimalarials. One derivative, 12-bromo premarineosin A, shows high potency against chloroquine-resistant Plasmodium falciparum (IC50 < 5 nM) with minimal cytotoxicity. The work addresses the urgent need for new antimalarial therapies as artemisinin-based combination therapies face rapid emergence of resistance. In vitro efficacy and selectivity testing will be conducted against both chloroquine-resistant and chloroquine-sensitive P. falciparum strains.

Work is performed at the University of Michigan, Ann Arbor, Michigan. The period of performance runs through July 31, 2028. The award is classified as a Project Grant under the assistance listing for infectious disease research, which supports biomedical research and research training at public and private nonprofit institutions.