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. 2020 Jan 22;25(3):460.
doi: 10.3390/molecules25030460.

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Qing Fang  1 , Fleurdeliz Maglangit  1   2 , Linrui Wu  1 , Rainer Ebel  1 , Kwaku Kyeremeh  3 , Jeanette H Andersen  4 , Frederick Annang  5 , Guiomar Pérez-Moreno  6 , Fernando Reyes  5 , Hai Deng  1
Affiliations

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Qing Fang et al. Molecules. .

Abstract

Streptomyces 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 Streptomyces 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) 1 together with five known compounds, cyclo-(L-Pro-Gly) 2, cyclo-(L-Pro-L-Phe) 3, cyclo-(L-Pro-L-Val) 4, cyclo-(L-Leu-Hyp) 5, and deferoxamine E 6. AHFA 1, 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 (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, 7-12 and six siderophores 13-18.

Keywords: AHFA; MMFs; Streptomyces sp. RK44; anticancer; antimalaria; methylenomycin; signalling molecules.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Isolated metabolites from Streptomyces sp. RK44. structures of which were elucidated by NMR. Structure of AHFA 1 with COSY (―) and key HMBC (→) correlations.
Figure 2
Figure 2
Comparison of the ahfa BGC in Streptomyces sp. RK44 with the mmf gene cluster on the SCP1 plasmid of S. coelicolor A3(2). Homologous genes are colored the same, and sequence identities between each of the encoded proteins are indicated in Table 2.
Scheme 1
Scheme 1
Proposed biosynthesis pathway of 1.
Figure 3
Figure 3
(A) A2058 cell treated with 50µg/mL staurosporine (B) A2058 cell treated with 50µg/mL AHFA 1 (C) A2058 cell treated with culture media. Cell viability was quantified by Aqueous One Solution Reagent by a colourimetric method for determining the number of viable cells in proliferation or cytotoxicity assays. A2058 cells were left untreated or were treated with AHFA 1 for 72 h and morphological changes of the cells were observed by light microscope (Scale bar 26 μm).
Figure 4
Figure 4
Phylogenetic analysis of 16S rDNA sequences of Streptomyces sp. RK44 and other known Streptomyces species, indicating that Streptomyces sp. RK44 is a new Streptomyces species.
See this image and copyright information in PMC

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