Discovery and Heterologous Production of Sarubicins and Quinazolinone C-Glycosides with Protecting Activity for Cardiomyocytes

Glycosylated natural products and their derivatives are important pharmaceutical agents. Genome mining of C-glycosylated metabolites biosynthetic gene cluster (BGC) from a soil-derived Streptomyces led to the isolation of sarubicins A (1) and B (2), of which 1 has a rare 2-oxabicyclo[2.2.2] substructure arising from C-glycosylation and C-C bond formation between aglycone and the C-4 position of deoxysugar. Heterologous expression of the sar BGC led to the production of sarubicins and three new C-glycosylated quinazolinones 3-5 with single C-C bond between aglycone and deoxysugar, indicating the stepwise formation mechanism of the two unusual C-C bonds. A convenient chemical transformation from 1 to 2 and a proposed biosynthetic pathway for sarubicins, were presented. Significantly, compounds 1 and 2 showed potent protective effects on the neonatal rat cardiomyocytes.