Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Qing Fang; Fleurdeliz Maglangit; Linrui Wu; Rainer Ebel; Kwaku Kyeremeh; Jeanette H. Andersen; Frederick Annang; Guiomar Perez de Nanclares; Fernando Reyes; Hai Deng

doi:10.3390/molecules25030460

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Qing Fang, Fleurdeliz Maglangit, Linrui Wu, Rainer Ebel, Kwaku Kyeremeh, Jeanette H. Andersen, Frederick Annang, Guiomar Perez de Nanclares, Fernando Reyes, Hai Deng^* (Corresponding Author)

^*Corresponding author for this work

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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.

Original language	English
Article number	460
Number of pages	13
Journal	Molecules
Volume	25
Issue number	3
DOIs	https://doi.org/10.3390/molecules25030460
Publication status	Published - 22 Jan 2020

Bibliographical note

Q.F. is grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM for financial support through the PEER/PERCE Funding. FM thanks the University of the Philippines for the Faculty, Reps and Staff Development Program (FRAS DP) for the PhD grant fellowship. HD and KK thank the financial supports of Leverhulme Trust-Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council-UK Department for International Development (MRC/DFID) Concordat agreement African Research Leaders Award (MR/S00520X/1).

Keywords

AHFA
methylenomycin
MMFs
signalling molecules
Streptomyces sp. RK44
anticancer
antimalaria
DESFERRIOXAMINE-E
DIKETOPIPERAZINES
ACID
IDENTIFICATION
ANTIBIOTIC PRODUCTION
Streptomyces sp
GROWTH
BACTERIUM
RK44
Signalling molecules
Antimalaria
Anticancer
Methylenomycin

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title = "Signalling and Bioactive Metabolites from Streptomyces sp. RK44",

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, methylenomycin, MMFs, signalling molecules, Streptomyces sp. RK44, anticancer, antimalaria, DESFERRIOXAMINE-E, DIKETOPIPERAZINES, ACID, IDENTIFICATION, ANTIBIOTIC PRODUCTION, Streptomyces sp, GROWTH, BACTERIUM, RK44, Signalling molecules, Antimalaria, Anticancer, Methylenomycin",

author = "Qing Fang and Fleurdeliz Maglangit and Linrui Wu and Rainer Ebel and Kwaku Kyeremeh and Andersen, {Jeanette H.} and Frederick Annang and {Perez de Nanclares}, Guiomar and Fernando Reyes and Hai Deng",

note = " Q.F. is grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM for financial support through the PEER/PERCE Funding. FM thanks the University of the Philippines for the Faculty, Reps and Staff Development Program (FRAS DP) for the PhD grant fellowship. HD and KK thank the financial supports of Leverhulme Trust-Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council-UK Department for International Development (MRC/DFID) Concordat agreement African Research Leaders Award (MR/S00520X/1).",

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AU - Fang, Qing

AU - Maglangit, Fleurdeliz

AU - Wu, Linrui

AU - Ebel, Rainer

AU - Kyeremeh, Kwaku

AU - Andersen, Jeanette H.

AU - Annang, Frederick

AU - Perez de Nanclares, Guiomar

AU - Reyes, Fernando

AU - Deng, Hai

N1 - Q.F. is grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM for financial support through the PEER/PERCE Funding. FM thanks the University of the Philippines for the Faculty, Reps and Staff Development Program (FRAS DP) for the PhD grant fellowship. HD and KK thank the financial supports of Leverhulme Trust-Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council-UK Department for International Development (MRC/DFID) Concordat agreement African Research Leaders Award (MR/S00520X/1).

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-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.

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-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.

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KW - ANTIBIOTIC PRODUCTION

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KW - Antimalaria

KW - Anticancer

KW - Methylenomycin

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DO - 10.3390/molecules25030460

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SN - 1420-3049

VL - 25

JO - Molecules

JF - Molecules

IS - 3

M1 - 460

ER -

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Abstract

Bibliographical note

Keywords

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