Metabolic engineering and late-stage functionalization expand the chemical space of the antimalarial premarineosin A.

ABSTRACT: Diversification of structurally complex natural products remains a key challenge in the discovery of next-generation therapeutics. Premarineosin A, a potent and selective antimalarial natural product, is a promising yet underexplored scaffold due to its limited availability and synthetic complexity. In this work, we overcome both barriers by coupling metabolic engineering with late-stage derivatization, enabling the first systematic exploration of the premarineosin A scaffold. Rational engineering of Streptomyces eitanensis, encoding a premarineosin A biosynthetic gene cluster, increased titers over 170-fold. Sustainable production of (-)-premarineosin A enabled a unique semi-synthetic and biocatalytic derivatization campaign. In this structure-activity relationship study of premarineosin

SUBMITTER: McBride CM 

PROVIDER: S-EPMC12680612 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature