Accramycin A, a New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

Fleurdeliz Maglangit (Corresponding Author), Qing Fang, Valentin Leman, Sylvia Soldatou, Rainer Ebel, Kwaku Kyeremeh, Hai Deng (Corresponding Author)

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Abstract

Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.
Original languageEnglish
Article number3384
JournalMolecules
Volume24
Issue number18
DOIs
Publication statusPublished - 17 Sep 2019

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Polyketides
Streptococcus agalactiae
Streptomyces
bacteria
soils
Bacteria
Carbazoles
Soil
Polyketide Synthases
streptococcus
Soils
Molecules
metabolites
Biosynthetic Pathways
Microbial Sensitivity Tests
Drug Discovery
Metabolites
Biological Products
Scaffolds
molecules

Keywords

  • accramycin
  • naphthacene
  • type II polyketide
  • Streptomyces sp. MA37
  • Group B streptococcus
  • BETA-LACTAM RESISTANCE
  • ANTIBIOTICS
  • CIRCUMVENTORS
  • NONPREGNANT ADULTS
  • DEREPLICATION
  • NATURAL-PRODUCTS
  • NEOCARAZOSTATIN
  • Streptomyces sp
  • Group B Streptococcus
  • BIOSYNTHESIS
  • NAPHTHACEMYCINS
  • B STREPTOCOCCAL DISEASE
  • MA37

Cite this

Accramycin A, a New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37. / Maglangit, Fleurdeliz (Corresponding Author); Fang, Qing; Leman, Valentin; Soldatou, Sylvia; Ebel, Rainer; Kyeremeh, Kwaku; Deng, Hai (Corresponding Author).

In: Molecules, Vol. 24, No. 18, 3384, 17.09.2019.

Research output: Contribution to journalArticle

Maglangit, Fleurdeliz ; Fang, Qing ; Leman, Valentin ; Soldatou, Sylvia ; Ebel, Rainer ; Kyeremeh, Kwaku ; Deng, Hai. / Accramycin A, a New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37. In: Molecules. 2019 ; Vol. 24, No. 18.
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AU - Ebel, Rainer

AU - Kyeremeh, Kwaku

AU - Deng, Hai

N1 - 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 MRC African Research Leaders Award (MR/S00520X/1). R.E. and S.S. are grateful to British Council/Newton Fund for financial support through the Institutional Links scheme (Project No. 261781172). QF is grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM for financial support through the PEER/PERCE Funding.

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N2 - Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.

AB - Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.

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