PCOMPBIOL-D-25-02043

Fitness advantage of sequential metabolic strategies emerges from community interactions in strongly fluctuating environments

PLOS Computational Biology

Dear Dr. Goyal,

Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Sandro Azaele

Academic Editor

PLOS Computational Biology

Zhaolei Zhang

Section Editor

PLOS Computational Biology

Additional Editor Comments:

The reviewers acknowledge that your manuscript presents a thought-provoking theoretical framework for understanding metabolic strategies in microbial communities. While one of them has no major concerns, the other one raises several concerns that require attention before the work can be accepted. The reviewer particularly questions the mechanistic explanation for why sequential utilizers succeed in communities despite resource depletion, and they note that your assumption of independent growth rates on different resources (no physiological trade-offs) may be overly idealized. Additionally, they find the switching between two fitness metrics potentially confusing for readers, and suggest that the "Top-Smart" assumption for sequential utilizers may artificially inflate their advantage. The paper needs more thorough exploration of key parameters (particularly the large dilution factor D), clearer connections to established theoretical frameworks for structural stability, and discussion of how results might generalize beyond the specific serial dilution scenario studied. I think that addressing these points and discussions will significantly strengthen the manuscript.

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: Yu Fu, Sergei Maslov, Akshit Goyal, and Zihan Wang. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: In this manuscript, Wang et al. study the competition between microbial species with different metabolic strategies in ecological communities under boom-and-bust cycles. For this, the authors develop a Consumer-Resource model that captures the cyclic arrival of nutrients into the system in a way analogous to serial dilutions experiments. Co-utilizing species divide their enzime budget—and therefore average their growht rate— among the available (or primary) resources, and sequential utilizers use resources one at a time, which can maximize growth rate on their preferred resource at a cost of a potential lag time when switching to another resource.

The paper was a pleasure to read, I found it insightful and well written. I especially appreciate the clear explanation on how smaller enzyme budget fractions allocated to every other primary resource favors sequential consumers in community context, the linear algebra approximation providing an interpretable prediction on the structural stability of niche-packed communities, and the experimentally testable predictions on the prevalence of sequential consumers in high diversity communities—left as a proposal for experimentalists to test in the future. I recommend this manuscript for publication in Plos Computational Biology, with just some minor potential changes. Below are some suggestions and small comments that I have.

MINOR COMMENTS:

I think that the second ‘=‘ sign in Eq. 1 is a typo. I would expect it to be replaced by a product sign ‘·’, or another functional form. Otherwise I don’t understand how both E^r =1 and E^m =1 maximize the growth rate, and an explanation should be given.

The model assumes top-smart sequential species. How would the relaxation of this assumption affect the results? Perhaps it would be interesting to compare with a top-random choice (or any other illustrative choice). Intuitively, this would make it more difficult to find competitive-enough sequential species, increasing the diversity of the species pool required to generate niche-packed communities. But I’d be interested in reading the interpretation—and potentially some analysis— of the authors.

Check the format of all references. For example, there’s a problem with the citation in line [291].

Another typo, this one about Sr in line 372

- Line 107, typo ‘…it takes TO deplete all…’. Check the text for other minor typos like this, e.g. line 122. . In the caption of Fig. S5, some quantity is said to ‘increase by a lot’, which was a bit funny to read (please replace by a more quantitative or rigorous vocabulary). Also in the same caption, ‘y=5’ but ‘y’ has not been defined as biomass fraction. Same caption, the description of panel c precedes the one of b.

- I think that the supplementary figures should be indexed according to their order of citation in the main text. Fig. S5 is the first one to be cited. I think most of the other supplementary figures are cited later in the main text, but I did not check if all of them are cited.

Thanks again for this reading, I found it very interesting.

Reviewer #2: Please see attached

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data and code should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes: Samraat Pawar & Yan Zhu

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Attachments

Attachment

Submitted filename: Review_of_Wang_et_al.pdf

PCOMPBIOL-D-25-02043R1

Fitness advantage of sequential metabolic strategies emerges from community interactions in strongly fluctuating environments

PLOS Computational Biology

Dear Dr. Goyal,

Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 08 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

* A letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.

* A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

* An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Sandro Azaele

Academic Editor

PLOS Computational Biology

Zhaolei Zhang

Section Editor

PLOS Computational Biology

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Note: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Reviewers' comments:

Reviewer's Responses to Questions

Reviewer #1: In my opinion, the authors have appropriatly addressed all the questions and suggestions from the referees. I recommend the current version for publication.

Reviewer #2: The revised manuscript presents a clear and conceptually strong contribution, extending consumer–resource models to incorporate dynamic proteome allocation and demonstrating an emergent ecological advantage of sequential metabolic strategies in diverse communities. The authors have addressed the major concerns from the first round effectively, including robustness to key assumptions (e.g. “top-smart” strategies, parameter trade-offs, dilution factor) and improved clarity around the fitness metrics and mechanisms.

We think work is now suitable for publication. However, a small number of minor clarifications and refinements would further strengthen the manuscript and improve accessibility:

* Clarify whether enzymes map one-to-one to substrates or allow multi-substrate use; briefly note implications for lag dynamics.

* Add a short, main-text explanation linking ϕ to microbial physiology and its limitations.

* Briefly signpost early that growth rate is mechanistic, while biomass prevalence is the ecological outcome.

* Include a one-line summary that results are robust (and even strengthened) under constrained efficiencies.

* Clarify more prominently that the mechanism relies on fluctuating environments and is unlikely in steady-state (e.g. chemostats).

* Define “mature communities” at first use.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data and code should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes: Samraat Pawar & Yan Zhu

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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While revising your submission, we strongly recommend that you use PLOS’s NAAS tool (https://ngplosjournals.pagemajik.ai/artanalysis) to test your figure files. NAAS can convert your figure files to the TIFF file type and meet basic requirements (such as print size, resolution), or provide you with a report on issues that do not meet our requirements and that NAAS cannot fix.

After uploading your figures to PLOS’s NAAS tool - https://ngplosjournals.pagemajik.ai/artanalysis, NAAS will process the files provided and display the results in the "Uploaded Files" section of the page as the processing is complete. If the uploaded figures meet our requirements (or NAAS is able to fix the files to meet our requirements), the figure will be marked as "fixed" above. If NAAS is unable to fix the files, a red "failed" label will appear above. When NAAS has confirmed that the figure files meet our requirements, please download the file via the download option, and include these NAAS processed figure files when submitting your revised manuscript.

Reproducibility:

To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Dear Goyal,

We are pleased to inform you that your manuscript 'Fitness advantage of sequential metabolic strategies emerges from community interactions in strongly fluctuating environments' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology.

Best regards,

Sandro Azaele

Academic Editor

PLOS Computational Biology

Zhaolei Zhang

Section Editor

PLOS Computational Biology

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