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A marine viral halogenase that iodinates diverse substrates.

ABSTRACT: Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage. Notably, halogenases have been previously associated with secondary metabolism, tailoring natural products. Exploration of this viral halogenase reveals it capable of regioselective halogenation of a diverse range of substrates with a preference for forming aryl iodide species; this has potential implications for the metabolism of the infected host. Until recently, a flavin-dependent halogenase that is capable of iodination in vitro had not been reported. VirX1 is interesting from a biocatalytic perspective as it shows strikingly broad substrate flexibility and a clear preference for iodination, as illustrated by kinetic analysis. These factors together render it an attractive tool for synthesis.

SUBMITTER: Gkotsi DS

PROVIDER: S-EPMC6875430 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A marine viral halogenase that iodinates diverse substrates.

Gkotsi Danai S DS Ludewig Hannes H Sharma Sunil V SV Connolly Jack A JA Dhaliwal Jagwinder J Wang Yunpeng Y Unsworth William P WP Taylor Richard J K RJK McLachlan Matthew M W MMW Shanahan Stephen S Naismith James H JH Goss Rebecca J M RJM

Nature chemistry 20191014 12

Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage. Notably, halogenases have been previously associated with secondary ...[more]

PMID: 31611633

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Project description:In host-associated bacteria, surface and secreted proteins mediate acquisition of nutrients, interactions with host cells, and specificity of tissue localization. In Gram-negative bacteria, the mechanism by which many proteins cross and/or become tethered to the outer membrane remains unclear. The domain of unknown function 560 (DUF560) occurs in outer membrane proteins throughout Proteobacteria and has been implicated in host-bacterium interactions and lipoprotein surface exposure. We used sequence similarity networking to reveal three subfamilies of DUF560 homologs. One subfamily includes those DUF560 proteins experimentally characterized thus far: NilB, a host range determinant of the nematode-mutualist Xenorhabdus nematophila, and the surface lipoprotein assembly modulators Slam1 and Slam2, which facilitate lipoprotein surface exposure in Neisseria meningitidis (Y. Hooda, C. C. Lai, A. Judd, C. M. Buckwalter, et al., Nat Microbiol 1:16009, 2016, https://doi.org/10.1038/nmicrobiol.2016.9; Y. Hooda, C. C. L. Lai, T. F. Moraes, Front Cell Infect Microbiol 7:207, 2017, https://doi.org/10.3389/fcimb.2017.00207). We show that DUF560 proteins from a second subfamily facilitate secretion of soluble, nonlipidated proteins across the outer membrane. Using in silico analysis, we demonstrate that DUF560 gene complement correlates with bacterial environment at a macro level and host association at a species level. The DUF560 protein superfamily represents a newly characterized Gram-negative secretion system capable of lipoprotein surface exposure and soluble protein secretion with conserved roles in facilitating symbiosis. In light of these data, we propose that it be titled the type 11 secretion system (TXISS). IMPORTANCE The microbial constituency of a host-associated microbiome emerges from a complex physical and chemical interplay of microbial colonization factors, host surface conditions, and host immunological responses. To fill unique niches within a host, bacteria encode surface and secreted proteins that enable interactions with and responses to the host and co-occurring microbes. Bioinformatic predictions of putative bacterial colonization factor localization and function facilitate hypotheses about the potential of bacteria to engage in pathogenic, mutualistic, or commensal activities. This study uses publicly available genome sequence data alongside experimental results from Xenorhabdus nematophila to demonstrate a role for DUF560 family proteins in secretion of bacterial effectors of host interactions. Our research delineates a broadly distributed family of proteins and enables more accurate predictions of the localization of colonization factors throughout Proteobacteria.

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A marine viral halogenase that iodinates diverse substrates.

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A marine viral halogenase that iodinates diverse substrates.

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