24 research outputs found

    Across the Fence: Analyzing the Trinity College HMCTA Partnership

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    #carenotcops with CT Black and Brown Student Union

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    This Community Action Gateway group worked with the CT Black and Brown Student Union (BBSU) #carenotcops campaign against policing in schools through data-driven research presented through a digestible infographic

    Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in lactococcus lactis

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    © 2016 John Wiley & Sons Ltd. The second messenger cyclic-di-adenosine monophosphate (c-di-AMP) plays important roles in growth, virulence, cell wall homeostasis, potassium transport and affects resistance to antibiotics, heat and osmotic stress. Most Firmicutes contain only one c-di-AMP synthesizing diadenylate cyclase (CdaA); however, little is known about signals and effectors controlling CdaA activity and c-di-AMP levels. In this study, a genetic screen was employed to identify components which affect the c-di-AMP level in Lactococcus. We characterized suppressor mutations that restored osmoresistance to spontaneous c-di-AMP phosphodiesterase gdpP mutants, which contain high c-di-AMP levels. Loss-of-function and gain-of-function mutations were identified in the cdaA and gdpP genes, respectively, which led to lower c-di-AMP levels. A mutation was also identified in the phosphoglucosamine mutase gene glmM, which is commonly located within the cdaA operon in bacteria. The glmM I154F mutation resulted in a lowering of the c-di-AMP level and a reduction in the key peptidoglycan precursor UDP-N-acetylglucosamine in L. lactis. C-di-AMP synthesis by CdaA was shown to be inhibited by GlmMI154F more than GlmM and GlmMI154F was found to bind more strongly to CdaA than GlmM. These findings identify GlmM as a c-di-AMP level modulating protein and provide a direct connection between c-di-AMP synthesis and peptidoglycan biosynthesis. c-di-AMP is an essential signalling molecule which affects peptidoglycan homeostasis and resistance against various stressors, however little is known regarding how the c-di-AMP level is regulated in the cell. Here we identify the peptidoglycan biosynthesis enzyme GlmM as a modulator of c-di-AMP synthesis through its regulation of diadenylate cyclase enzyme CdaA activity in Lactococcus lactis

    A genomics-guided study of the biosynthesis of microbial secondary metabolites

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    Microorganisms such as filamentous fungi and actinomycetes are prolific producers of structurally diverse secondary metabolites. Many microbial natural products have been developed into commercially valuable compounds such as pharmaceutical agents. After several decades of screening for bioactive compounds, the field of microbial natural product discovery is plagued with the problem of re-discovering already known compounds. To circumvent this challenge, we took a genomics-guided approach in this study to uncover the secondary metabolite synthesizing potential of the filamentous fungus Aspergillus westerdijkiae and the rare actinomycetes Nocardia jinanensis. The genome sequencing and characterization of certain secondary metabolism gene clusters described in this study sets the stage for exploring the full biosynthetic potential of the two highly prolific producers of secondary metabolite for the discovery of novel natural products and biosynthetic enzymes.DOCTOR OF PHILOSOPHY (SBS

    Complete genome sequence of the filamentous fungus Aspergillus westerdijkiae reveals the putative biosynthetic gene cluster of ochratoxin A

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    Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae, a major producer of OTA, reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins.MOE (Min. of Education, S’pore)Published versio

    Draft genome sequence of Nocardia jinanensis, an opportunistic bacterial pathogen that causes cellulitis

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    The draft genome sequence of Nocardia jinanensis, an opportunistic pathogen that can cause skin infections, reveals genes that may contribute to the lifestyle and pathogenicity of N. jinanensis. The genome also reveals the biosynthetic capacity of N. jinanensis in producing mycolic acids, siderophores, and other polyketide and nonribosomal peptide-derived secondary metabolites.Published versio

    Additional file 8: Table S12. of Sequencing and functional annotation of the whole genome of the filamentous fungus Aspergillus westerdijkiae

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    Structural and functional annotations of the OTA biosynthesis-related clusters on scaffold14 of A. westerdijkiae. Table S13. Structural and functional annotations of the OTA biosynthesis-related cluster on scaffold45 of A. westerdijkiae. (DOCX 153 kb
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