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Title: | Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides | Authors: | Maranha, Ana Costa, Mafalda Ripoll-Rozada, Jorge Manso, José A. Miranda, Vanessa Mendes, Vera M. Manadas, Bruno Macedo-Ribeiro, Sandra Ventura, M. Rita Pereira, Pedro José Barbosa Empadinhas, Nuno |
Issue Date: | 27-Jan-2023 | Publisher: | Springer Nature | Project: | This work was funded by Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia through projects PTDC/BIA-MIC/0122/2021, UIDB/04539/2020, UIDP/04539/ 2020 and LA/P/0058/2020; through PhD Fellowship SFRH/BD/101191/2014 (to M.C.); through contract POCI-01-0145-FEDER-029221 (to A. M.); through contract DL 57/2016/ CP1355/CT0011 (to J.R.-R.) and by the European Social Fund through Programa Operacional Capital Humano in the form of Postdoctoral Fellowship SFRH/BPD/108004/2015 (to J.R.-R.) and by the European Regional Development Fund (FEDER) through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020 in the form of grant POCI-01-0145-FEDER-029221, and the National Mass Spectrometry Network (RNEM) under the contract POCI-01-0145-FEDER- 402-022125 (ref.: ROTEIRO/0028/2013). M.R.V. acknowledges MostMicro Research Unit, financially supported by LISBOA-01-0145-FEDER-007660 funded by FEDER funds through COMPETE2020 (POCI) and by national funds through FCT. The NMR data was acquired at CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016 | Serial title, monograph or event: | Communications Biology | Volume: | 6 | Issue: | 1 | Abstract: | The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed α-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1→4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature. | URI: | https://hdl.handle.net/10316/111616 | ISSN: | 2399-3642 | DOI: | 10.1038/s42003-023-04448-3 | Rights: | openAccess |
Appears in Collections: | IIIUC - Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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