Application of Enzymes in Regioselective and Stereoselective Organic Reactions
, Max C. Wamsley 1, Colbee N. Duke 1, Payton H. Lii 1, Sarah E. Epley 1, London C. Todd 1 and Patty J. Roberts 1Round 1
Reviewer 1 Report
The manuscript sent by Mu et al. entitled "Application of enzymes in regioselective and stereoselective organic reactions" concerns a very important and interesting topic in catalysis - biocatalysis.The article is written in a clear and understandable way and the authors have adopted a logical division into types of catalysed reactions. The selection of literature is appropriate and logical, there are no unnecessary citations.It's a pity that the authors, apart from streo and regioselative reactions, were not tempted to show streospecific reactions, which are also important in particular in biomedical sciences .In the last years, the growing importance of the use of enzymes immobilized on various supports is observed. Such catalytic systems allows for example, the reuse of the catalyst and the creation of cascade systems. Moreover, the use of micelles and encapsulation are also in new trends in biocatalysts. In my opinion the authors should add to the review the section describing the use of enzymes immobilized on the carrier surface or encapsulated. Such reactions are currently in the trend of modern catalysis and should be included in the work.Despite the fact that the work is written in a transparent way, the authors did not avoid several editorial errors.
- Using the "Figure" and "Scheme" notation creates a slight mess. It would be better if instead of, for example, Figure 1 Scheme1, use the notation: Figure 1 (a), (b) ... or simply sign the individual reactions as Scheme1, Scheme 2 ... without "Figure".
- The arrows in the diagrams should be of such length that the reagent name fits completely over the arrow. This will improve the aesthetics of the Schemes.
- Where possible, enter the value % ee or % dd in the Schemes under the product.
- Scheme 21 shows an unnaturally long C=C bond, which must be corrected.
- In Scheme 15, arrows for MAO-N oxidation are very unclear, this needs to be improved.
- Authors should pay attention to the correct notation of stereochemical descriptors: cis, trans, R, S,γ, β should be in italics.
- Authors should read the article carefully and correct all typos such as for ex. ? transaminase (Scheme 28), 50?C (Figure 11) Pictet Spengler (L.148) ...
Author Response
We would like to thank the referee for the time spent to consider our work for publication in the Catalysts journal. We have replayed to all questions and remarks and our answers could be found below:
The manuscript sent by Mu et al. entitled "Application of enzymes in regioselective and stereoselective organic reactions" concerns a very important and interesting topic in catalysis - biocatalysis.The article is written in a clear and understandable way and the authors have adopted a logical division into types of catalysed reactions. The selection of literature is appropriate and logical, there are no unnecessary citations.
It's a pity that the authors, apart from streo and regioselative reactions, were not tempted to show streospecific reactions, which are also important in particular in biomedical sciences .In the last years, the growing importance of the use of enzymes immobilized on various supports is observed. Such catalytic systems allows for example, the reuse of the catalyst and the creation of cascade systems. Moreover, the use of micelles and encapsulation are also in new trends in biocatalysts. In my opinion the authors should add to the review the section describing the use of enzymes immobilized on the carrier surface or encapsulated. Such reactions are currently in the trend of modern catalysis and should be included in the work. Despite the fact that the work is written in a transparent way, the authors did not avoid several editorial errors.
Response: Thank you for the suggestion. We have already supplemented relative information about enzyme immobilization and encapsulation. Since this article has been through a major revision. We did not highlight the changes. We want to apologize in advance and thank you for your time and effort.
- Using the "Figure" and "Scheme" notation creates a slight mess. It would be better if instead of, for example, Figure 1 Scheme1, use the notation: Figure 1 (a), (b) ... or simply sign the individual reactions as Scheme1, Scheme 2 ... without "Figure".
Response: We appreciate your comment. We have deleted all “Figures” and signed the reactions as “Schemes”.
- The arrows in the diagrams should be of such length that the reagent name fits completely over the arrow. This will improve the aesthetics of the Schemes.
Response: We have improved all the schemes according to your suggestion.
- Where possible, enter the value % eeor % dd in the Schemes under the product.
Response: We have added relative parameters.
- Scheme 21 shows an unnaturally long C=C bond, which must be corrected.
Response: We have already corrected the error. We apologize for the confusion and our negligence.
- In Scheme 15, arrows for MAO-N oxidation are very unclear, this needs to be improved.
Response: Thank you for pointing that out. We have already changed the format of the arrows.
- Authors should pay attention to the correct notation of stereochemical descriptors: cis, trans, R, S,γ, βshould be in italics.
Response: We have done the change for the descriptors. Thank you for your advice. Once again we apologize for our negligence.
- Authors should read the article carefully and correct all typos such as for ex. ? transaminase (Scheme 28), 50?C (Figure 11) Pictet Spengler (L.148) ...
Response: We have already corrected all the typos. We apologize for the confusion and our imprudence
Reviewer 2 Report
- Abstract:
- …”..Biocatalysts..” - ..”biocatalysts..” - capital letter why?
- optimization of enzymes..” – defined features of enzymes are optimized e.g. activity…or others – this is too general shortcut
- Introduction:
- generally is a little bit outdated, because Authors should link the chirality and the optical purity with the nature of biological processes in general, not only with the thalidomide case.
- insulin is not an enzyme!!!
- there is no word about the disadvantages of using enzymes!! There are many of them – this issue should be extended, especially in the area of costs of biocatalysts isolation or production by genetically modified organisms also immobilizations, stability under non -physiological conditions and so on..
- herbicides are not only inorganics!
General remarks:
In my opinion text should be reorganized by introducing the paragraphs connected to the particular enzymes classes, because in the present form is hard to understand for readers and looks disorderly, especially that the same class of enzymes can be found in many parts of the textbody e.g. lipases
- Every enzyme should be classified by their nomenclature in accordance to E.C.
This is absolutely necessary, because in the text, there are examples of e.g. lipases applications for the C-C bond formation, while theses are hydrolases from the 3 class. That is why it is very important to clarify the path of the reaction and to point the exact step, which is catalysed by enzymes.
- Also – it is important to stress, what are the crucial conditions, which force the enzymes to catalyse particular reactions, in many cases opposite to their native specificity.
- These review requires some short discussion for every applied example – a specially if the biocatalysis is compared to particular chemical reaction.
- There is not such words as: oxidoreductations or catalysation! par. 2.2.1.
- The title: 2.2. Reactions without new covalent bond forming – should be improved, because dawn through the text there are examples of bond forming reactions, even reduction of the carbon functionality creates the new covalent bond between the oxygen and hydrogen atoms! Unless Authors meant the C-C bond formation??
- Schemes should be unified by adding the properly drawn bonds around the centre of chirality!!
Author Response
We would like to thank the referee for the time spent to consider our work for publication in the Catalysts journal. We have replayed to all questions and remarks and our answers could be found below:
- Abstract:
- …”..Biocatalysts..” - ..”biocatalysts..” - capital letter why?
Response: It is a typo, we apologize for the confusion and our negligence.
- optimization of enzymes..” – defined features of enzymes are optimized e.g. activity…or others
Response: We appreciate your comment. We have added the defined features as suggested
– this is too general shortcut
Response: Thank you for this comment. We did update our abstract. So it’s suitable and more specific for our review article.
- Introduction:
- generally is a little bit outdated, because Authors should link the chirality and the optical purity with the nature of biological processes in general, not only with the thalidomide case.
Response: That’s a great suggestion. We have described the stereoselectivity in the biosynthesis of melanin and norepinephrine, which could be used to elucidate the importance of the link between chirality and the nature of biological processes.
- insulin is not an enzyme!!!
Response: We have revised it by using another example. Thank you for your advice.
- there is no word about the disadvantages of using enzymes!! There are many of them – this issue should be extended, especially in the area of costs of biocatalysts isolation or production by genetically modified organisms also immobilizations, stability under non -physiological conditions and so on..
Response: Thank you for your comments. We have added the drawbacks of enzymes accordingly.
- herbicides are not only inorganics!
Response: We want to elucidate that enzyme could help to produce some inorganics which could be used as herbicides. In case the description makes confusion, we chose an example of the inorganics produced with the aid of the enzymes which could be employed to treat wastewater.
General remarks:
In my opinion text should be reorganized by introducing the paragraphs connected to the particular enzymes classes, because in the present form is hard to understand for readers and looks disorderly, especially that the same class of enzymes can be found in many parts of the textbody e.g. lipases
- Every enzyme should be classified by their nomenclature in accordance to E.C.
This is absolutely necessary, because in the text, there are examples of e.g. lipases applications for the C-C bond formation, while theses are hydrolases from the 3 class. That is why it is very important to clarify the path of the reaction and to point the exact step, which is catalysed by enzymes.
Response: Thank you for the great comments. Originally, we tried to establish a new system to clearly classify all the reactions depending on whether there is a new covalent bond forming. If a new covalent bond forming (C-C or C-N or C-O or C-S), we put the reaction into the new group. However, it seemed that the new system makes the manuscript disorganized. According to the traditional classification method, we have re-grouped all the reactions. Since this article has been through a major revision. We did not highlight the changes. We want to apologize in advance and thank you for your time and effort.
- Also – it is important to stress, what are the crucial conditions, which force the enzymes to catalyse particular reactions, in many cases opposite to their native specificity.
Response: Thank you for pointing that out. We have added the crucial conditions either in the scheme or in the context.
- These review requires some short discussion for every applied example – a specially if the biocatalysis is compared to particular chemical reaction.
Response: That’s a great suggestion. We have added a brief discussion before the applied examples.
- There is not such words as: oxidoreductations or catalysation! par. 2.2.1.
Response: They are typos. We apologize for the confusion and our imprudence.
- The title: 2.2. Reactions without new covalent bond forming – should be improved, because dawn through the text there are examples of bond forming reactions, even reduction of the carbon functionality creates the new covalent bond between the oxygen and hydrogen atoms! Unless Authors meant the C-C bond formation??
Response: Thank you for this comment. In the beginning, we tried to classify the reactions based on the C-C or C-N or C-O bond formation. If there is an extra bond like C-C/C-N/C-O formed on the substrate, we put the reaction in the “reactions with new covalent bond forming”. If there is no new bond formation, like reduction or oxidation, we put in this group. However, it seemed that this method of classification made the manuscript disorganized. So, we re-organized all the reactions according to the E.C. number.
- Schemes should be unified by adding the properly drawn bonds around the centre of chirality!!
Response: We have corrected/edited the schemes according to your suggestions.
Round 2
Reviewer 1 Report
Thanks to the Authors for including the comments. After the correction, this manuscript is suitable for publication in Catalysts in my opinion.
