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.
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We thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no. 614779 GenoChemetics to R.J.M.G.), Syngenta and Wellcome ISSF (grant no. 204821/Z/16/Z to D.S.G.) for generous financial support. We thank G. Harris and M. Weckener (Harwell) for size-excluion chromatography multiangle light scattering and analytical ultracentrifugation analysis. We thank all of our colleagues, in particular, T. Smith and co-workers in the School of Chemistry and the Biomedical Sciences Research Complex at the University of St Andrews for all of the help that they have afforded us in the aftermath of the BMS fire. We thank I. M. Wilson for assistance with graphics.
The authors declare no competing interests.
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Gkotsi, D.S., Ludewig, H., Sharma, S.V. et al. A marine viral halogenase that iodinates diverse substrates. Nat. Chem. 11, 1091–1097 (2019). https://doi.org/10.1038/s41557-019-0349-z
Angewandte Chemie International Edition (2021)
Journal of Medicinal Chemistry (2021)
Angewandte Chemie (2021)