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Cited by 47Microbial Natural Products and BiosynthesisMicrobial Metabolism and ApplicationsMarine Sponges and Natural Products

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A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

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Maglangit, Fleurdeliz, Fang, Qing, Kyeremeh, Kwaku, Sternberg, Jeremy M., Ebel, Rainer, Deng, Hai·2020·Molecules
DOI 10.3390/molecules25020256PMC PMC7024260
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Abstract

Whole-genome sequence data of the genus Streptomyces have shown a far greater chemical diversity of metabolites than what have been discovered under typical laboratory fermentation conditions. In our previous natural product discovery efforts on Streptomyces sp. MA37, a bacterium isolated from the rhizosphere soil sample in Legon, Ghana, we discovered a handful of specialised metabolites from this talented strain. However, analysis of the draft genome of MA37 suggested that most of the encoded biosynthetic gene clusters (BGCs) remained cryptic or silent, and only a small fraction of BGCs for the production of specialised metabolites were expressed when cultured in our laboratory conditions. In order to induce the expression of the seemingly silent BGCs, we have carried out a co-culture experiment by growing the MA37 strain with the Gram-negative bacterium Pseudomonas sp. in a co-culture chamber that allows co-fermentation of two microorganisms with no direct contact but allows exchange of nutrients, metabolites, and other chemical cues. This co-culture approach led to the upregulation of several metabolites that were not previously observed in the monocultures of each strain. Moreover, the co-culture induced the expression of the cryptic indole alkaloid BGC in MA37 and led to the characterization of the known indolocarbazole alkaloid, BE-13793C 1. Neither bacterium produced compound 1 when cultured alone. The structure of 1 was elucidated by Nuclear Magnetic Resonance (NMR), mass spectrometry analyses and comparison of experimental with literature data. A putative biosynthetic pathway of 1 was proposed. Furthermore, BE-13793C 1 showed strong anti-proliferative activity against HT-29 (ATCC HTB-38) cells but no toxic effect to normal lung (ATCC CCL-171) cells. To the best of our knowledge, this is the first report for the activity of 1 against HT-29. No significant antimicrobial and anti-trypanosomal activities for 1 were observed. This research provides a solid foundation for the fact that a co-culture approach paves the way for increasing the chemical diversity of strain MA37. Further characterization of other upregulated metabolites in this strain is currently ongoing in our laboratory.

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Metadata

Authors
Maglangit, F., Fang, Q., Kyeremeh, K., Sternberg, J. M., Ebel, R., & Deng, H.
Affiliations
  • University of the Philippines Cebu (PH)
  • University of Aberdeen (GB)
  • University of Ghana (GH)
Corresponding author
  • Maglangit, Fleurdeliz
  • Deng, Hai
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2020-01-08
Volume
25
Issue
2
Pages
256
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules25020256
PMC
PMC7024260
OpenAlex
W2999177106
Cited by
47
References
0
Citations by year
2026: 5 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 6
FWCI
4.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the University of the Philippines (the Faculty, Reps and Staff Development Program)
  • Leverhulme Trust (AA090088)
  • Medical Research Council (MR/S00520X/1)
  • British Council (261781172)
  • the University of Aberdeen (Elphinstone Scholarship)
  • Scottish Funding Council/ScotCHEM (PEER/PERCE Funding)
Topics
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
Keywords
co-culture, indole alkaloids, biosynthetic gene clusters, Pseudomonas, natural product discovery, structure elucidation, biosynthetic pathway, antiproliferative activity, HT-29 cells, rhizosphere bacteria
MeSH terms
Anti-Bacterial Agents, Biological Assay, Chromatography, High Pressure Liquid, Multigene Family, Humans, Microbial Sensitivity Tests, Pseudomonas, Trypanosoma, Cell Death, Biofilms, Coculture Techniques, HT29 Cells, Indole Alkaloids, Cell Proliferation, Biosynthetic Pathways, Metabolome, Proton Magnetic Resonance Spectroscopy

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