Identification of the minimal bacterial 2'-deoxy-7-amido-7-deazaguanine synthesis machinery

Molecular Microbiology
Yifeng YuanValérie de Crécy-Lagard

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 D...Continue Reading

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Citations

Sep 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yifeng YuanValérie de Crécy-Lagard
Dec 1, 2019·Nature Communications·Geoffrey HutinetValérie de Crécy-Lagard
Apr 16, 2019·Frontiers in Microbiology·Kiersten FlodmanShuang-Yong Xu
Aug 17, 2020·The Journal of Biological Chemistry·Janani PrahladMark A Wilson
Jul 25, 2021·International Journal of Molecular Sciences·Monika ŠimoliūnienėEugenijus Šimoliūnas

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