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A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing

Ximing Chen, Shuyan Li, Binglin Zhang, Haili Sun, Jinxiu Wang, Wei Zhang, Wenbo Meng, Tuo Chen, Paul Dyson Orcid Logo, Guangxiu Liu

Nucleic Acids Research, Volume: 50, Issue: 12, Pages: 7084 - 7096

Swansea University Author: Paul Dyson Orcid Logo

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DOI (Published version): 10.1093/nar/gkac502

Abstract

We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing...

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Published in: Nucleic Acids Research
ISSN: 0305-1048 1362-4962
Published: Oxford University Press (OUP) 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa60219
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The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. 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spelling 2023-04-13T10:39:13.9628402 v2 60219 2022-06-14 A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing 300e3f46b70ae83f563b24f41d00cd17 0000-0002-0558-2666 Paul Dyson Paul Dyson true false 2022-06-14 BMS We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing during translation. The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. Circumventing this by expression of the new cognate tRNA offers a generic strategy to increase antibiotic yields and to expand the repertoire of much-needed new bioactive metabolites produced by these valuable bacteria. Journal Article Nucleic Acids Research 50 12 7084 7096 Oxford University Press (OUP) 0305-1048 1362-4962 8 7 2022 2022-07-08 10.1093/nar/gkac502 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University West Light Foundation of The Chinese Academy of Sciences (xbzg-zdsys-202105); the National Key R&D Program of China (2019YFE0121100); the National Science Foundation of China (31870479); UK BBSRC China Partnering Grant [BB/J020419/1]; The National Key Research and Development Program of China (2020YFC2006600); Gansu Youth Science and Technology Fund Program (20JR5RA207). 2023-04-13T10:39:13.9628402 2022-06-14T12:37:18.8258391 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Ximing Chen 1 Shuyan Li 2 Binglin Zhang 3 Haili Sun 4 Jinxiu Wang 5 Wei Zhang 6 Wenbo Meng 7 Tuo Chen 8 Paul Dyson 0000-0002-0558-2666 9 Guangxiu Liu 10 60219__24414__31a72c4766534787886c2bde13353d42.pdf 60219.pdf 2022-06-29T16:22:43.0879919 Output 1855473 application/pdf Version of Record true Copyright: The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/),
title A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
spellingShingle A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
Paul Dyson
title_short A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
title_full A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
title_fullStr A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
title_full_unstemmed A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
title_sort A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
author_id_str_mv 300e3f46b70ae83f563b24f41d00cd17
author_id_fullname_str_mv 300e3f46b70ae83f563b24f41d00cd17_***_Paul Dyson
author Paul Dyson
author2 Ximing Chen
Shuyan Li
Binglin Zhang
Haili Sun
Jinxiu Wang
Wei Zhang
Wenbo Meng
Tuo Chen
Paul Dyson
Guangxiu Liu
format Journal article
container_title Nucleic Acids Research
container_volume 50
container_issue 12
container_start_page 7084
publishDate 2022
institution Swansea University
issn 0305-1048
1362-4962
doi_str_mv 10.1093/nar/gkac502
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing during translation. The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. Circumventing this by expression of the new cognate tRNA offers a generic strategy to increase antibiotic yields and to expand the repertoire of much-needed new bioactive metabolites produced by these valuable bacteria.
published_date 2022-07-08T04:18:09Z
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