Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens
Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de nov...
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2020
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| Online Access: | https://hdl.handle.net/1721.1/124461 |
| _version_ | 1811096726944088064 |
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| author | Dedon, Peter C. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dedon, Peter C. |
| author_sort | Dedon, Peter C. |
| collection | MIT |
| description | Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de novo synthesis, salvage of the prokaryotic Q precursors preQ0 and preQ1 also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ0 and preQ1, the enzymes and transporters involved in Q salvage and recycling have not been well described. We discovered and characterized 2 Q salvage pathways present in many pathogenic and commensal bacteria. The first, found in the intracellular pathogen Chlamydia trachomatis, uses YhhQ and tRNA guanine transglycosylase (TGT) homologs that have changed substrate specificities to directly salvage q, mimicking the eukaryotic pathway. The second, found in bacteria from the gut flora such as Clostridioides difficile, salvages preQ1 from q through an unprecedented reaction catalyzed by a newly defined subgroup of the radical-SAM enzyme family. The source of q can be external through transport by members of the energy-coupling factor (ECF) family or internal through hydrolysis of Q by a dedicated nucleosidase. This work reinforces the concept that hosts and members of their associated microbiota compete for the salvage of Q precursors micronutrients. |
| first_indexed | 2024-09-23T16:48:05Z |
| format | Article |
| id | mit-1721.1/124461 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:48:05Z |
| publishDate | 2020 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1244612022-09-29T21:35:32Z Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens Dedon, Peter C. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Center for Environmental Health Sciences Multidisciplinary Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de novo synthesis, salvage of the prokaryotic Q precursors preQ0 and preQ1 also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ0 and preQ1, the enzymes and transporters involved in Q salvage and recycling have not been well described. We discovered and characterized 2 Q salvage pathways present in many pathogenic and commensal bacteria. The first, found in the intracellular pathogen Chlamydia trachomatis, uses YhhQ and tRNA guanine transglycosylase (TGT) homologs that have changed substrate specificities to directly salvage q, mimicking the eukaryotic pathway. The second, found in bacteria from the gut flora such as Clostridioides difficile, salvages preQ1 from q through an unprecedented reaction catalyzed by a newly defined subgroup of the radical-SAM enzyme family. The source of q can be external through transport by members of the energy-coupling factor (ECF) family or internal through hydrolysis of Q by a dedicated nucleosidase. This work reinforces the concept that hosts and members of their associated microbiota compete for the salvage of Q precursors micronutrients. United States. Department of Energy (Contract No. DE-AC02-06CH11357) 2020-03-31T18:57:30Z 2020-03-31T18:57:30Z 2019-09-03 2020-02-12T18:27:08Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/124461 Yuan, Yifeng et al. "Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens." Proceedings of the National Academy of Sciences of the United States of America 116 (2019):19126-19135 © 2019 The Author(s) en 10.1073/pnas.1909604116 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Multidisciplinary Dedon, Peter C. Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title | Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title_full | Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title_fullStr | Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title_full_unstemmed | Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title_short | Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| title_sort | discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens |
| topic | Multidisciplinary |
| url | https://hdl.handle.net/1721.1/124461 |
| work_keys_str_mv | AT dedonpeterc discoveryofnovelbacterialqueuinesalvageenzymesandpathwaysinhumanpathogens |