Signalling and bioactive metabolites from Streptomyces sp. RK44

Abstract

<i>Streptomyces</i> remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of <i>Streptomyces</i> sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) together with five known compounds, cyclo-(L-Pro-Gly), cyclo-(L-Pro-L-Phe), cyclo-(L-Pro-L-Val), cyclo-(L-Leu-Hyp), and deferoxamine E. AHFA, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC₅₀ = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (<i>ahfa</i>) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC₅₀ = 1.08 µM) against <i>P. falciparum</i> 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, and six siderophores.