Modelling and Multi-Criteria Decision Making for Selection of Specific Growth Rate Models of Batch Cultivation by Saccharomyces cerevisiae Yeast for Ethanol Production
Round 1
Reviewer 1 Report
In this ms. Petrov focused on Multi Criteria Decision Making (MCDM) for selection of specific growth rate models of batch cultivation of Saccharomyces cerevisiae. The author uses the Promethee method to determine the ranking of the analyzed models. Although this is an interesting study, it is unclear what the overall message is since the simulation curves of ten models are indistinguishable from each other. In this regard, it is essential to provide an experimental example showing that the Andrews model, the highest ranked, is clearly superior to the others.
Additional comments:
1) There is no explanation why the simulation gave identical results for all of the models and it is slightly different from experimental data (Fig 1C).
2) It is not clear to me why the author insists with the Tessiermodel in the abstract and the conclusion, despite that the Andrews was found to be the highest ranked.
3) Abstract: Is it the Tessier model that can be used in the future? The sentence “It will be used to model and optimise the process” is vague and sound like a future plan rather than a conclusion from the presented data. Please remove it.
4) Introduction: It is unclear what is known from the author’s previous publications and what has been done in the present ms.
5) The language used in the ms must be professionally edited because the usage of tenses is often incorrect. In particular, please use present tense for well established facts but not to describe how the experiments were performed in this ms. (e.g. “for all of them we choose smaller weights”). I also noticed colloquial or awkward sentences such as “is not an easy task”, “Andrewsmodel (M6) is the highest ranking”, “the research was conducted in 5L laboratory bioreactor”, as well as typos (e.g. “Tape” instead of Type and “Pomethee”).
Author Response
Response to Reviewer 1 Comments
Many thanks to the Reviewer for the time spent and the effort he or she have made in reviewing my manuscript (MS). The remarks and comments have helped me a lot to improve it.
In this MS. Petrov focused on Multi Criteria Decision Making (MCDM) for selection of specific growth rate models of batch cultivation of Saccharomyces cerevisiae. The author uses the PROMETHEE method to determine the ranking of the analyzed models. Although this is an interesting study, it is unclear what the overall message is since the simulation curves of ten models are indistinguishable from each other. In this regard, it is essential to provide an experimental example showing that the Andrews model, the highest ranked, is clearly superior to the others.
Response: As explained in MS, all models were adequate and could be used to model the process (Line 215 and 216). Unfortunately, I do not have any additional data to test both the selected Andrews model and each of the rest.
Point 1: There is no explanation why the simulation gave identical results for all of the models and it is slightly different from experimental data (Fig 1C).
Response 1: The figures were small in scale and these inconspicuous differences were not significant. Therefore, I applied the PROOMETHEE method to choose the most appropriate one with the fewest errors in simulating the results. For the sake of clarity at the end (before Conclusion) of MS I showed the model of the process (1) - (3) with the Andrews model for a specific growth rate. Additionally, figures of experimental and simulated results and the resulting Residuals for all the ten models were included. Andrews's model was the best one for them.
Point 2: It is not clear to me why the author insists with the Tessier model in the abstract and the conclusion, despite that the Andrews was found to be the highest ranked.
Response 2: I wanted to show that the Tessier model also be used. In order to avoid confusion however this part was removed from the study. The model for the specific growth rate with the highest rank was selected.
Point 3: Abstract: Is it the Tessier model that can be used in the future? The sentence “It will be used to model and optimise the process” is vague and sound like a future plan rather than a conclusion from the presented data. Please remove it.
Response 3: It was removed.
Point 4: Introduction: It is unclear what is known from the author’s previous publications and what has been done in the present MS.
Response 4: In our previous publications [11-16], which are quoted in the Introduction, we mainly deal with modelling, optimization and optimal control of two mixing systems, impulse mixing and vibromixing, where modelling is used for the functional state approach and several global models. Therefore, in this MS, I decided to do a more complete study of the process through global models and experimental studies at the Institute of Technical Chemistry, University of Hannover, Germany.
Point 5: The language used in the ms must be professionally edited because the usage of tenses is often incorrect. In particular, please use present tense for well established facts but not to describe how the experiments were performed in this ms. (e.g. “for all of them we choose smaller weights”). I also noticed colloquial or awkward sentences such as “is not an easy task”, “Andrews model (M6) is the highest ranking”, “the research was conducted in 5L laboratory bioreactor”, as well as typos (e.g. “Tape” instead of Type and “Pomethee”).
Response 5: These errors were corrected. MS was given to a professional reviewer for more in-depth English corrections.
I hope I have responded fully to all the remarks!
With Respect
Mitko Petrov
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript "Modelling and Multi Criteria Decision Making for Selection of Specific Growth Rate Models of Batch Cultivation by Saccharomyces cerevisiae yeast for Ethanol Production" investigates on the optimization of ethanol production by S. cerevisiae in glucose as carbon source. The topic is of in interest by there are some concerns that fixed.
The main concern is the data of Table 2 are calculated. The row data?
In the methodologies section should be better described the modalities of batch fermentation trials (row data , repetitions ) and conditions applied ( biomass evaluation dry weight??, air v/v/min......)
Figures 1-3 in the test are reported as Figures 1 a , b , c, this is unclear. Moreover it is not clear how the simulated data obtained from the specific growth rate models could be used for ethanol and glucose simulated data showed in f1gures 1 b and 1c ( or fig 2 and fig 3)
Line 54 Saccharomyces cerevisiae italic and after S. cerevisiae through the manuscript
Line 77 bacteria?? Yeast
line 98 as below
Author Response
Response to Reviewer 2 Comments
Many thanks to the Reviewer for the time spent and the effort he or she has made in reviewing my manuscript (MS). The remarks and comments made have helped me a lot to improve it.
Point 1: The main concern is the data of Table 2 are calculated. The row data?
Response 1: The minimization criterion (4) was calculated for the specific values of the parameters in the (1)-(3) and M1-M10 models (shown in Table 2) by using the developed algorithm and programme.
Point 2: In the methodologies section should be better described the modalities of batch fermentation trials (row data, repetitions) and conditions applied (biomass evaluation dry weight??, air v/v/min......)
Response 2: Few details are given on the conditions of cultivation of Saccharomyces cerevisiaes. Detailed conditions of cultivation, preparation of culture medium, etc., are shown in the supplementary book included in the Reference: Pencheva, T.; Roeva, O.; Hristozov, I. “Description of the examined fermentation processes of Sacchromyces cerevisiae and Escherichia coli”, as well as the book Functional state approach to fermentation processes modeling; St. Tzonkov, B. Hitzmann, Eds.; Prof. Marin Drinov Academic Publishing House, Sofia, Bulgaria, 2006, pp. 51-56.
Point 3: Figures 1-3 in the test are reported as Figures 1 a , b , c, this is unclear. Moreover it is not clear how the simulated data obtained from the specific growth rate models could be used for ethanol and glucose simulated data showed in f1gures 1 b and 1c (or fig 2 and fig 3)
Response 3: A purely technical error that was corrected. Only Figures 1a, 1b, and 1c remain. The simulated data shown in Figures 1a, 1b and 1c was calculated using the developed program. The program finally calculated the simulated data shown in Figure 1 for each of the (1)-(3) and M1 - M10 models in addition to the minimization criterion (4), the parameters in the models (1) - (3) and M1 – M10 and the criteria Cj. In addition, for clarity, MS included the Andrews model in the process model (10) - (12).
Point 4: Line 54 Saccharomyces cerevisiae italic and after S. cerevisiae through the manuscript
Response 4: Corrected in MS.
Point 5: Line 77 bacteria?? Yeast
Response 5: Corrected in MS.
Point 6: line 98 as below
Response 6: Corrected in MS.
I hope I have responded fully to all the remarks!
With Respect
Mitko Petrov
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
I am satisfied with the author's appeal.
Author Response
Many thanks to the Reviewer for the time spent and the effort he or she have made in reviewing my manuscript (MS). The remarks and comments have helped me a lot to improve it.
Point 1: English language and style are fine/minor spell check required
Response 1: Dear Reviewer, I have done everything possible to improve the English language of MS. MS has been sent for English editing once more.
I hope I have responded fully to all the remarks!
With Respect
Mitko Petrov
Author Response File: Author Response.pdf
Reviewer 2 Report
The revised version of the manuscript "Modelling and Multi Criteria Decision Making for Selection of Specific Growth Rate Models of Batch Cultivation by Saccharomyces cerevisiae yeast for Ethanol Production" still shows some concerns:
The main concern regarding to the data of Table 2 are not fixed and further explanations should be presented not only the inclusion of bibliography. Some differences in sugar concentrations in the Material and Methods section are showed.
The response to point 2 is limited. The reference to a " supplementary book included in the Reference: Pencheva, T.; Roeva, O.; Hristozov, I. “Description of the examined fermentation processes of Sacchromyces cerevisiae and Escherichia coli”, as well as the book Functional state approach to fermentation processes modeling; St. Tzonkov, B. Hitzmann, Eds.; Prof. Marin Drinov Academic Publishing House, Sofia, Bulgaria, 2006, pp. 51-56." is not sufficient. More details in the manuscript needed.
"Line 54 Saccharomyces cerevisiae italic and after S. cerevisiae through the manuscript" this mistake is nor fixed
Author Response
Response to Reviewer 2 (Round 2) Comments
Many thanks to the Reviewer for the time spent and the effort he or she has made in reviewing my manuscript (MS). The remarks and comments have helped me a lot to improve it.
The revised version of the manuscript “Modelling and Multi Criteria Decision Making for Selection of Specific Growth Rate Models of Batch Cultivation by Saccharomyces cerevisiae yeast for Ethanol Production” still shows some concerns:
Point 1: The main concern regarding to the data of Table 2 are not fixed and further explanations should be presented not only the inclusion of bibliography. Some differences in sugar concentrations in the Material and Methods section are showed.
Response 1: In Table 2, I noticed errors that have been fixed. Additionally I have included the search intervals for each of the estimated parameters in the models before Table 2 in the text . A very short comment on the yield coefficients – YS/X and YS/E, which are almost equal, is added after the table. In the revised version there are no differences in glucose concentrations (Material and Methods).
Point 2: The response to point 2 is limited. The reference to a “supplementary book included in the Reference: Pencheva, T.; Roeva, O.; Hristozov, I. “Description of the examined fermentation processes of Sacchromyces cerevisiae and Escherichia coli”, as well as the book Functional state approach to fermentation processes modeling; St. Tzonkov, B. Hitzmann, Eds.; Prof. Marin Drinov Academic Publishing House, Sofia, Bulgaria, 2006, pp. 51-56.” is not sufficient. More details in the manuscript needed.
Response 2: In the revised version of MS The rest of the information regarding2.1. Process specific is included in the cited literature [17]. I do not have more batch processing details.
Point 3: “Line 54 Saccharomyces cerevisiae italic and after S. cerevisiae through the manuscript” this mistake is now fixed
Response 3: I cannot understand what would like from me to do. Saccharomyces cerevisiae is italic in the entire MS (including line 54).
I hope I have responded fully to all the remarks!
With Respect
Mitko Petrov
Author Response File: Author Response.pdf
