Identification of the minimal bacterial 2′-deoxy-7-amido-7-deazaguanine synthesis machinery
Name
nihms-987035.pdf
Description
Accepted version
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1.41 MB
Format
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Checksum (MD5)
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Author(s)
Valera, Jacqueline Gamboa
Hu, Jennifer
Hillebrand, Roman
Dedon, Peter C.
Date Issued
October 12, 2018
Journal
Molecular microbiology
Publisher
Wiley
Citation
Yuan, Yifeng et al. “Identification of the minimal bacterial 2′-deoxy-7-amido-7-deazaguanine synthesis machinery.” Molecular microbiology 110 (2018): © 2018 The Author(s)
Version
Author's final manuscript
Abstract
The 7-deazapurine derivatives, 2′-deoxy-7-cyano-7-deazaguanosine (dPreQ0) and 2′-deoxy-7-amido-7-deazaguanosine (dADG) are recently discovered DNA modifications encoded by the dpd cluster found in a diverse set of bacteria. Here we identify the genes required for the formation of dPreQ0 and dADG in DNA and propose a biosynthetic pathway. The preQ0 base is a precursor that in Salmonella Montevideo, is synthesized as an intermediate in the pathway of the tRNA modification queuosine. Of the 11 genes (dpdA – dpdK) found in the S. Montevideo dpd cluster, dpdA and dpdB are necessary and sufficient to synthesize dPreQ0, while dpdC is additionally required for dADG synthesis. Among the rest of the dpd genes, dpdE, dpdG, dpdI, dpdK, dpdD and possibly dpdJ appear to be involved in a restriction-like phenotype. Indirect competition for preQ0 base led to a model for dADG synthesis in which DpdA inserts preQ0 into DNA with the help of DpdB, and then DpdC hydrolyzes dPreQ0 to dADG. The role of DpdB is not entirely clear as it is dispensable in other dpd clusters. Our discovery of a minimal gene set for introducing 7-deazapurine derivatives in DNA provides new tools for biotechnology applications and demonstrates the interplay between the DNA and RNA modification machineries.
Subjects
Molecular Biology
Microbiology
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Singapore-MIT Alliance in Research and Technology (SMART)
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1111/mmi.14113
