TY - JOUR
T1 - Signalling and bioactive metabolites from Streptomyces sp. RK44
AU - Fang, Qing
AU - Maglangit, Fleurdeliz
AU - Wu, Linrui
AU - Ebel, Rainer
AU - Kyeremeh, Kwaku
AU - Andersen, Jeanette H.
AU - Annang, Frederick
AU - Pérez-Moreno, Guiomar
AU - Reyes, Fernando
AU - Deng, Hai
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
PY - 2020/1/22
Y1 - 2020/1/22
N2 - 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-LeuHyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited antiproliferative 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.
AB - 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-LeuHyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited antiproliferative 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.
KW - AHFA
KW - Anticancer
KW - Antimalaria
KW - MMFs
KW - Methylenomycin
KW - Signalling molecules
KW - Streptomyces sp. RK44
UR - http://www.scopus.com/inward/record.url?scp=85078236633&partnerID=8YFLogxK
U2 - 10.3390/molecules25030460
DO - 10.3390/molecules25030460
M3 - Article
C2 - 31979050
AN - SCOPUS:85078236633
SN - 1420-3049
VL - 25
JO - Molecules
JF - Molecules
IS - 3
M1 - 460
ER -