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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa60219
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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 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.
College: Swansea University Medical School
Funders: 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).
Issue: 12
Start Page: 7084
End Page: 7096