Genomic scanning enabling discovery of a new antibacterial bicyclic carbamate-containing alkaloid

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dc.contributor.authorFang, Q.
dc.contributor.authorWu, L.
dc.contributor.authorUrwald, C.
dc.contributor.authorMugat, M.
dc.contributor.authorWang, S.
dc.contributor.authorKyeremeh, K.
dc.contributor.authorPhilips, C.
dc.contributor.authorLaw, S.
dc.contributor.authorZhou, Y.
dc.contributor.authorDeng, H.
dc.date.accessioned2021-03-03T14:33:41Z
dc.date.available2021-03-03T14:33:41Z
dc.date.issued2021
dc.descriptionResearch Articleen_US
dc.description.abstractNon-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical applications. Bacterial pyrrolizidine alkaloids (PAs), containing a scaffold of two fused fivemembered ring system with a nitrogen atom at the bridgehead, have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates, followed by multistep oxidation, catalysed by single Bayer-Villiger (BV) enzymes, to yield PA scaffolds. Although bacterial PAs are rare in natural product inventory, bioinformatics analysis suggested that the biosynthetic gene clusters (BGCs) that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial genomes. However, most of the strains containing PA-like BGCs are not deposited in the public domain, therefore preventing further assessment of the chemical spaces of this group of bioactive metabolites. Here, we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome information. Among the strains tested, we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring formation. Subsequently one-strain-many-compound (OSMAC) method, supported by a combination of HR-MS, NMR, SMART 2.0 technology, and GNPS analysis, allowed identification and characterization of a new [5 + 7] heterobicyclic carbamate, legoncarbamate, together with five known PAs, bohemamine derivatives, from Streptomyces sp. CT37, a Ghanaian soil isolate. The absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD spectra. Legoncarbamate displays antibacterial activity against E. coli ATCC 25922 with an MIC value of 3.1 μg/mL. Finally, a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.en_US
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/36090
dc.language.isoenen_US
dc.publisherSynthetic and Systems Biotechnologyen_US
dc.subjectGenomic scanningen_US
dc.subjectBayer villiger monooxygenaseen_US
dc.subjectCarbamate alkaloidsen_US
dc.subjectPyrrolizidine alkaloidsen_US
dc.subjectNon-ribosomal peptide synthetasesen_US
dc.titleGenomic scanning enabling discovery of a new antibacterial bicyclic carbamate-containing alkaloiden_US
dc.typeArticleen_US

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