Abstract:
Abstract: Drug-like molecules are known to contain many di erent building blocks with great
potential as pharmacophores for drug discovery. The continued search for unique sca olds in
our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37.
This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines,
and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a
new naphthacene-type aromatic natural product, which wehave named accramycinA1. This molecule
was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular
networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D
NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus
(GBS) produced a minimum inhibitory concentration (MIC) of 27 g/mL. This represents the first
report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the
possibility for the further development of potent molecules against GBS based on the accramycin
sca old. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type
II polyketide synthase, was proposed.
