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

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dc.contributor.authorKyeremeh, K.
dc.contributor.authorMaglangit, F.
dc.contributor.authorFang, Q.
dc.contributor.authorSternberg, J.M.
dc.contributor.authorEbel, R.
dc.contributor.authorDeng, H.
dc.date.accessioned2020-02-03T12:29:55Z
dc.date.available2020-02-03T12:29:55Z
dc.date.issued2020-01-08
dc.descriptionResearch Articleen_US
dc.description.abstractWhole-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 e orts 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 e ect 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.en_US
dc.description.sponsorshipUniversity of the Philippines Faculty, Reps, and Sta Development Program (FRAS DP) for the PhD grant fellowship. H.D. and K.K. are grateful for the financial support of the 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). R.E. is grateful to British Council/Newton Fund for financial support through the Institutional Links scheme (Project No. 261781172). Q.F. is grateful to the University of Aberdeen Elphinstone Scholarship and the Scottish Funding Council/ScotCHEM for financial support through PEER/PERCE Fundingen_US
dc.identifier.otherdoi:10.3390/molecules25020256
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/34770
dc.language.isoenen_US
dc.publishermoleculesen_US
dc.relation.ispartofseries25;256
dc.subjectsilent genesen_US
dc.subjectcryptic genesen_US
dc.subjectco-cultureen_US
dc.subjectStreptomyces sp. MA37en_US
dc.subjectPseudomonas spen_US
dc.subjectindolocarbazoleen_US
dc.subjectalkaloiden_US
dc.titleA Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metaboliteen_US
dc.typeArticleen_US

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