Signalling and Bioactive Metabolites from <i>Streptomyces</i> sp. RK44
Qing Fang,
Fleurdeliz Maglangit,
Linrui Wu,
Rainer Ebel,
Kwaku Kyeremeh,
Jeanette H. Andersen,
Frederick Annang,
Guiomar Pérez-Moreno,
Fernando Reyes,
Hai Deng
Affiliations
Qing Fang
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
Fleurdeliz Maglangit
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
Linrui Wu
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
Rainer Ebel
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
Kwaku Kyeremeh
Marine and Plant Research Laboratory of Ghana, Department of Chemistry, University of Ghana, P.O. Box LG56 Legon, Accra, Ghana
Jeanette H. Andersen
Marbio, UiT—The Arctic University of Norway, N-9037 Tromsø, Norway
Frederick Annang
Fundación MEDINA, Avda. del Conocimiento 34, 18016 Armilla, Granada, Spain
Guiomar Pérez-Moreno
Instituto de Parasitología y Biomedicina “López-Neyra”, Consejo Superior de Investigaciones Científicas (CSIC) Avda. del Conocimiento 17, 18016 Armilla, Granada, Spain
Fernando Reyes
Fundación MEDINA, Avda. del Conocimiento 34, 18016 Armilla, Granada, Spain
Hai Deng
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
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 = 1.08 µM) 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.
