Journal article 38 views 3 downloads
A new bacterial tRNA enhances antibiotic production in <i>Streptomyces</i> by circumventing inefficient wobble base-pairing
Nucleic Acids Research, Volume: 50, Issue: 12, Pages: 7084 - 7096
Swansea University Author: Paul Dyson
PDF | Version of Record
Copyright: The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution LicenseDownload (1.77MB)
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...
|Published in:||Nucleic Acids Research|
Oxford University Press (OUP)
Check full text
No Tags, Be the first to tag this record!
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.
Swansea University Medical School
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).