Peer Review History

Original SubmissionApril 15, 2020
Decision Letter - Christopher N. Boddy, Editor

PONE-D-20-10863

The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic.

PLOS ONE

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Christopher N. Boddy, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript describes the identification and characterization of the biosynthetic gene cluster for tetromadurin from Actinomadura verrucosispora. The authors present a thorough biosynthetic proposal based upon bioinformatic analysis of the gene cluster alongside several strategic gene inactivation experiments. Comparisons are drawn to the previously studied tetronasin and tetronomycin pathways.

The manuscript is well written with only a couple of very minor typographic errors and describes sound, high quality experimental research.

Publication is recommended after these minor changes.

Line 81-83: How were the necessary building blocks determined? Was this previously reported? Based on labelling experiments? Or is this a prediction?

Line 192: Add information about the MS parameters used for HPLC-MS analysis

Line 213-214: Include information in methods section about how the Actinomadura verrucosispora was sequenced. Include gDNA isolation and sequencing preparation steps as well as genome assembly information. If this was carried out by a service, state which company/lab

Figures 4/5: would benefit from using colour to highlight chemical changes in the structures. Also hard to read the writing inside circles in Fig 4, remove shading in circles.

Line 282-285: These two sentences feel out of place a confusing. Either remove entirely or rephrase and move to after the description of the PKS genes that are present.

Line 300-303: The use of the term “predicted” to describe both of the structures in Fig 6 caption is confusing and inconsistent with the statement in line 292-294 in the text. Please clarify language

Line 421: Change “(Fig 8c)” to “(Fig 9c)”

Line 500-502: Can you really use this argument if the complementation worked for Mad10 using the same vector?

Line 533: Change “Fig 7” to “Fig 8”

Line 756: Change “oolyether” to “polyether”

Reviewer #2: Little et al identified the biosynthetic gene cluster involved in polyether compound tetromadurin biosynthesis in Actinomadura verrucosispora. They did bioinformatic analysis and performed gene deletions (cyclase genes mad10 and mad31) to confirm the involvement of this cluster in tetromadurin biosynthesis. The overall writing is clear. The following issues are suggested to be addressed:

The biggest issue is that the novel tetromadurin analogue produced by Δmad10 was not purified and identified by NMR analysis.

Fig 4, 5: please combine these two figures. For Fig 4, I would like to suggest the authors to use different colors to indicate the specificities of the ATs.

Fig 6: It is more appropriate to remove Fig 6 to supporting information as this product is predicted via bioinformatics analysis.

In the section of “Genes for (2R)-methoxymalonyl-ACP biosynthesis”, line 381-382, tautomycin and oxazolomycin are suggested to be referred as well.

Fig 9: It is more appropriate to remove Fig 9 to supporting information.

S13 Fig: more PyrE3 homologues are suggested to be subjected to phylogenetic analysis.

Line 987: “Fig Alignment of” should be “S14 Fig Alignment of” The accession numbers of protein sequences for alignment are suggested to be added.

Please number all the compounds in the manuscript.

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Reviewer #1: No

Reviewer #2: No

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Revision 1

Please see attached .pdf document for our response.

Attachments
Attachment
Submitted filename: Response to reviewers.pdf
Decision Letter - Patrick C. Cirino, Editor

The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic.

PONE-D-20-10863R1

Dear Dr. Little,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Patrick C. Cirino

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Patrick C. Cirino, Editor

PONE-D-20-10863R1

The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic

Dear Dr. Little:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Patrick C. Cirino

Academic Editor

PLOS ONE

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