Whole-genome sequencing of the Streptomyces coelicolor bldA39 mutant (J1700) of reveals hundreds of previously unknown mutations.
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We report the genome sequence of the bldA39 (J1700) mutant Streptomyces coelicolor, a historically important strain that is deficient in sporulation and antimicrobial production. The S. coelicolor J1700 strain was used extensively from the 1980s onwards to underpin important discoveries in development and antibiotic production in Streptomyces. The bldA gene encodes a leucyl transfer RNA (tRNA), required for the translation of the rare TTA codon found in ~2% of genes in Streptomyces. The whole genome of S. coelicolor J1700 was obtained via Illumina sequencing and mapped to the of S. coelicolor M145 reference genome. Analysis of the genome sequence compared to S. coelicolor M145 identified the known bldA39 mutation (T>C) and revealed more than 300 further mutations, likely associated with the S. coelicolor J1501 genetic background the strain was created in, including the nature of the hisA1 and uraA1 alleles used extensively in genetic mapping experiments and several mutations in natural product biosynthetic gene clusters. This work highlights the importance of whole genome sequencing of historically important strains.
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Thank you very much for the quick submission of your revised manuscript and for applying the suggested corrections. I am pleased to let you know that this current version has now been accepted for publication, I am sure it will be of great interest to the Streptomyces research community. Congratulations to all authors!
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thank you very much for submitting your manuscript to Access Microbiology. It has now been reviewed by two experts in the field, whose comments are attached at the bottom of this email. They both agree that this is a valuable contribution to the field that sheds light on the behaviours of a historical mutant strain of S. coelicolor from a genomic point of view. However, some minor corrections need to be applied before progressing to publication. Please introduce the reviewer suggested amendments. I would also like to double-check the title of the manuscript, as I believe there is a typo ("...the Streptomyces coelicolor bldA39 mutant (J1700) OF reveals..."). Please submit a revised version of the manuscript (including a tracked changes document) along with a point-by-point response tot he reviewer suggestions by January 31st 2025
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Comments to Author
This study revisits the historically significant Streptomyces coelicolor J1700 (bldA39 mutant), a model strain pivotal in understanding morphological differentiation and antibiotic production. Through whole-genome sequencing, the researchers uncovered over 300 mutations, including the bldA39 mutation, which disrupts translation of rare TTA codons, impairing development and secondary metabolism. The analysis clarified genetic markers for auxotrophies and resolved discrepancies in earlier studies, especially regarding antibiotic biosynthetic gene clusters. By combining historical context with modern genomic tools, this research highlights the strain's enduring importance and provides a valuable resource for advancing studies on microbial development and optimizing antibiotic production. I have some …
Comments to Author
This study revisits the historically significant Streptomyces coelicolor J1700 (bldA39 mutant), a model strain pivotal in understanding morphological differentiation and antibiotic production. Through whole-genome sequencing, the researchers uncovered over 300 mutations, including the bldA39 mutation, which disrupts translation of rare TTA codons, impairing development and secondary metabolism. The analysis clarified genetic markers for auxotrophies and resolved discrepancies in earlier studies, especially regarding antibiotic biosynthetic gene clusters. By combining historical context with modern genomic tools, this research highlights the strain's enduring importance and provides a valuable resource for advancing studies on microbial development and optimizing antibiotic production. I have some suggestions for improving the text on several places 1. line 19: "mutant OF Streptomyces ...." 2. lines 57-59: rephrase. Phenotypes are not mapped 3. line 64: make the uuA all capitals 4. line 67: rephrase. I think the authors refer to the presence of TTA codons in pathway-specific key regulators of the BGCs 5. line 76: "...copy of THE bldA gene..." 6. line 81: unclear: a genotype is indicated that is bldA-dependent? 7. line 93: were should be was 8. Line 96: Could the authors clarify whether paired-end libraries were used for sequencing? 9. line 107: Kieser et al., [20] 10. line 124. I would suggest "loss of the SCO6353-SCO6406 genes" 11. line 149: add "the" in between "in" and "S. coelicolor" 12. line 173: cpkBbeta?
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
The authors describe a deep investigation into the Streptomyces coelicolor bldA mutant - so-called because the strain grows without development of aerial hyphae and spores. The work goes a layer deeper into this pleiotropic mutant and identifies approximately 300 mutations resulting from the background of the strain. The data is well-curated and meets all of the journal's requirements for making datasets public access. The work provides a great historic overview of the origin of the bldA mutant, as well as positioning the importance of this work within the broader context of Streptomyces for the production of antibiotics and for the study of bacterial genetic regulation. The work provides a deep level of insight into the mutations in the strain and is an excellent example of how Illumina sequencing can …
Comments to Author
The authors describe a deep investigation into the Streptomyces coelicolor bldA mutant - so-called because the strain grows without development of aerial hyphae and spores. The work goes a layer deeper into this pleiotropic mutant and identifies approximately 300 mutations resulting from the background of the strain. The data is well-curated and meets all of the journal's requirements for making datasets public access. The work provides a great historic overview of the origin of the bldA mutant, as well as positioning the importance of this work within the broader context of Streptomyces for the production of antibiotics and for the study of bacterial genetic regulation. The work provides a deep level of insight into the mutations in the strain and is an excellent example of how Illumina sequencing can be used to shed a light on systems biology, providing insights into several phenotypic observations with S. coelicolor J1700 - e.g., lower undecylprodigiosin production, an unusual anticodon change from leucine to serine, mutation in the histinol dehydrogenase gene. The work is impeccably described and written and provides an excellent resource for the community. I have no corrections to suggest, only that the paper should be accepted forthwith in its current form.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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