Catenulisporolides, glycosylated triene macrolides from the chemically underexploited actinomycete Catenulispora species = 희귀방선균 카테누리스포라로부터 항말라리아 활성을 지니는 카테누리스포로로이드 발굴

Abstract

New glycosylated 26-membered triene macrolides catenulisporolides, the first polyketide metabolites from Catenulispora species, were obtained by targeting slow-forming colonies on selection agar plates and applying long-term cultivation. Their structures, including the full stereochemistry, were defined by comprehensive spectroscopic and chemical methods and confirmed by bioinformatics analysis. Analysis of the genome sequence revealed the responsible biosynthetic gene cluster spanning ∼160 kbp, and feeding experiments with isotope-labeled precursors showed that isovaleric acid acts as a rare starter unit. Catenulisporolides exhibited antimalarial activities against resistant strains of Plasmodium falciparum, and enhanced activity was observed in semisynthetic derivatives.