Signal Molecules Regulate the Synthesis of Secondary Metabolites in the Interaction between Endophytes and Medicinal Plants

Round 1

Reviewer 1 Report

Although the manuscript is an interesting topic, it is not clearly written for non-specialist readers. The representation of the generic structures of the treated compounds could help a better understanding.
It would be appreciated if the conclusions were separated from the prospects since it is very long and unclear.

Author Response

Response Letter

Dear Reviewer,

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. We hope that our work can be improved again. Furthermore, we would like to show the details as follows:

Reviewer 1:

1. Although the manuscript is an interesting topic, it is not clearly written for non-specialist readers.

Reply: Thank you for your suggestion. With regard to your constructive suggestions, after carefully reviewing the manuscript, we have rearranged the language of the manuscript and improved the deficiencies of the manuscript. Some sentences and grammar problems that are too long and difficult to understand have been revised to make the manuscript more readable. The specific revised sentences are as follows:

1. We changed "Furthermore, the destruction of wild medicinal resources as well as unplanned and unregulated exploitation caused by the wave of economic development have exacerbated the extreme scarcity of herbal resources and have significantly contributed to the formation of global resource scarcity concerns" to "In addition, the wave of economic development has also brought about the destruction of wild medicinal resources and unplanned and unregulated exploitation. This has accelerated the formation of the global shortage of herbal resources". Please refer to lines 34-37 of the revised manuscript and change the track.
2. We changed"The plant genome encodes hundreds of structurally specific membrane-associated pattern recognition receptors (PRRs) [21], and specific PRRs are required for the recognition of microbial-associated molecular pattern (MAMP) signals in the symbiosis pathway, which includes nitrogenous polysaccharide-based biopolymers such as chitosan, bacterial extracellular polysaccharide (EPS) [22], lipopolysaccharide (LPS) [23], and various protein components, etc" to "Plant genomes encode hundreds of structure-specific membrane-associated pattern recognition receptors (PRRs) [21] to specifically recognize microbial associated molecular patterns (MAMP). MAMPs that play a role in symbiotic pathway include chitosan, bacterial extracellular polysaccharide (EPS) [22], lipopolysaccharide (LPS) [23] and various protein components". Please refer to lines 104-108 of the revised manuscript and change the track.
3. We changed" Among them, calcium ions (Ca²⁺), reactive oxygen species (ROS), jasmonic acid (JA), salicylic acid (SA), and some other interlocking signaling systems play a particularly prominent role. These signaling molecules integrate through a signaling network that conducts external stimuli to various transcription factors (TFs), and the different transcription factors will activate the relevant products to synthesize the genes" to "Among them, hydrogen peroxide (H₂O₂), jasmonic acid (JA), salicylic acid (SA) and other signal molecules have special chemical structures(Figure 1) and key effects. Together with other messengers such as calcium signaling system, they play a particularly prominent role". Please refer to lines 135-138 of the revised manuscript and change the track.
4. We changed" It was pointed out by the study that in plant cells, the activation effect of phenylalanine deaminase acting by endophytic bacterial inducers can be inhibited by catalase, and superoxide dismutase (SOD) can inhibit the promotion of secondary metabolite synthesis by inducers of antitoxin-like species" to " It is pointed out that in plant cells, catalase can inhibit the activation of phenylalanine deaminase by endophytic inducers, and superoxide dismutase (SOD) can inhibit the promotion of antitoxin inducers on the synthesis of secondary metabolites ". Please refer to lines 219-222 of the revised manuscript and change the track.
5. We changed" SA itself is converted to free radicals to undergo lipid peroxidation and enhances the signal through its peroxidation and a self-feedback mechanism of oxidation products with and SA, causing NPR1, TGA and WRKY, and other transcription factors to activate and interact [100], ultimately inducing PRs gene expression and allergic response, development of systemic acquired resistance and accumulation of secondary metabolites" to "SA enhances the signal through its own peroxidation and self-feedback mechanism of oxidation products. Intracellular signaling triggers the activation and interaction of transcription factors such as NPR1, TGA, and WRKY [101], which ultimately induce the expression of PRs genes and the development of allergic responses, leading to the development of acquired resistance and the accumulation of secondary metabolites in the host". Please refer to lines 255-260 of the revised manuscript and change the track.
6. We changed" It was pointed out by the study that in plant cells, the activation effect of phenylalanine deaminase acting by endophytic bacterial inducers can be inhibited by catalase, and superoxide dismutase (SOD) can inhibit the promotion of secondary metabolite synthesis by inducers of antitoxin-like species" to " It is pointed out that in plant cells, catalase can inhibit the activation of phenylalanine deaminase by endophytic inducers, and superoxide dismutase (SOD) can inhibit the promotion of antitoxin inducers on the synthesis of secondary metabolites ". Please refer to lines 219-222 of the revised manuscript and change the track.
7. We changed" Related studies revealed that NO may be located in the upstream position of the JA pathway, and NO-specific scavenger (cPTIO) and lipoxygenase inhibitor (NDGA) can inhibit the promotion of JA synthesis by Aspergillus niger cell wall inducers and the synthesis of plant secondary metabolites by NO, respectively " to " Related studies found that NO-specific scavengers (cPTIO) could inhibit the promotion of JA synthesis by Aspergillus niger cell wall inducers and lipoxygenase inhibitors (NDGA) could inhibit the effect of NO on the synthesis of plant secondary metabolites[103]. It is thus speculated that NO may be located in the upstream position of the JA pathway ". Please refer to lines 273-278 of the revised manuscript and change the track.
8. We changed" Therefore, it is necessary to systematically study the metabolic and regulatory pathways of specific endophytes within a large group of microorganisms to analyze the specific physiological patterns of plant responses to endophytes during the intercropping process and the differences in the intercropping between different taxa and host plants, to screen for more efficient endophytic species to further improve the quality of medicinal herbs " to " Therefore, it is necessary to conduct systematic studies on the metabolic pathways and regulatory pathways of specific endophytic bacteria within a large group of microorganisms. To further analyze the specific physiological patterns of plant responses to endophytes during the intercropping process. Through the differences in the interactions between different taxa and host plants, more efficient endophytic species can be selected to improve the quality of medicinal herbs ". Please refer to lines 353-359 of the revised manuscript and change the track.
9. The representation of the generic structures of the treated compounds could help a better understanding.

Reply: Thank you for your kind suggestions. With regard to your constructive comments, we also corrected the deficiencies of the manuscript, and illustrated the general crystal structure and molecular characteristics of the processed compounds, which helps to better understand the role of the processed compounds. Please refer to Table 1 of the revised manuscript and change the track.

3. It would be appreciated if the conclusions were separated from the prospects since it is very long and unclear.

Reply: Thank you for your kind advice. With regard to your constructive comments, after careful examination, we have separated the conclusion from the prospect. And we have also improved the contents of the two parts respectively to make the text structure clearer. For the revisions in the conclusion part, please refer to the track changes in lines 310-323 of the revised version. For the prospects revision, please refer to the track change in lines 324-391 of the revised version.

 

 

And thank you very much for your attention and time. Look forward to hearing from you.

Sincerely yours,

Prof. Dr. Delin Xu

February 28, 2023

Reviewer 2 Report

Dear author, this work is really great. nevertheless, I would like you to review the headings of column 2 (types) of table 1.

 

Author Response

Dear Reviewer,

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. We hope that our work can be improved again. Furthermore, we would like to show the details as follows:

 

Reviewer 2:

1. Dear author, this work is really great. nevertheless, I would like you to review the headings of column 2 (types) of table 1.

Reply: Thank you for taking time to review our manuscript and your positive comments. With your kind suggestion, we have changed the headings of column 2 of Table 1 from "types" to "Action category". Please refer to Table 1 on page 5 of the revised manuscript with track change.

 

Thank you very much for your attention and time. Look forward to hearing from you.

 

Sincerely yours,

Prof. Dr. Delin Xu

February 28, 2023

Reviewer 3 Report

This review article provides a comprehensive and valuable analysis of the role of endophytic bacteria in promoting the synthesis and accumulation of secondary metabolites in medicinal plants. The authors make a strong case for the need to explore this subject matter, given the challenges associated with extracting and separating natural active compounds, the limitations of artificial synthesis, and the global scarcity of herbal resources. The article provides a detailed overview of the mechanisms that allow endophytic bacteria to regulate plant growth and development, including the important role played by signaling molecules. The authors focus on exploring the symbiotic mutualism system between endophytic bacteria and medicinal plants and the molecular mechanisms of signal transduction involved. The article provides valuable insights into the types and characteristics of signaling molecules in medicinal plants and the multi-molecular cross-talk during interactions between endophytic bacteria and medicinal plants. Overall, this review provides valuable ideas for the effective synthesis of medicinal ingredients using endophytic bacteria. However, the article could be further improved by avoiding unclear long sentences and checking for grammar mistakes. With these improvements, the article could make a valuable contribution to the literature and be a useful reference for researchers working in the field.

Author Response

Dear Reviewers，

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. We hope that our work can be improved again. Furthermore, we would like to show the details as follows:

Reviewer 3:

1. The article could be further improved by avoiding unclear long sentences and checking for grammar mistakes.

Reply: Thank you for your suggestion. With regard to your constructive suggestions, after carefully reviewing the manuscript, we have rearranged the language of the manuscript and improved the deficiencies of the manuscript. Some sentences and grammar problems that are too long and difficult to understand have been revised to make the manuscript more readable. The specific revised sentences are as follows:

We changed "Furthermore, the destruction of wild medicinal resources as well as unplanned and unregulated exploitation caused by the wave of economic development have exacerbated the extreme scarcity of herbal resources and have significantly contributed to the formation of global resource scarcity concerns" to "In addition, the wave of economic development has also brought about the destruction of wild medicinal resources and unplanned and unregulated exploitation. This has accelerated the formation of the global shortage of herbal resources". Please refer to lines 34-37 of the revised manuscript and change the track.

We changed"The plant genome encodes hundreds of structurally specific membrane-associated pattern recognition receptors (PRRs) [21], and specific PRRs are required for the recognition of microbial-associated molecular pattern (MAMP) signals in the symbiosis pathway, which includes nitrogenous polysaccharide-based biopolymers such as chitosan, bacterial extracellular polysaccharide (EPS) [22], lipopolysaccharide (LPS) [23], and various protein components, etc" to "Plant genomes encode hundreds of structure-specific membrane-associated pattern recognition receptors (PRRs) [21] to specifically recognize microbial associated molecular patterns (MAMP). MAMPs that play a role in symbiotic pathway include chitosan, bacterial extracellular polysaccharide (EPS) [22], lipopolysaccharide (LPS) [23] and various protein components". Please refer to lines 104-108 of the revised manuscript and change the track.

We changed "Among them, calcium ions (Ca²⁺), reactive oxygen species (ROS), jasmonic acid (JA), salicylic acid (SA), and some other interlocking signaling systems play a particularly prominent role. These signaling molecules integrate through a signaling network that conducts external stimuli to various transcription factors (TFs), and the different transcription factors will activate the relevant products to synthesize the genes" to "Among them, hydrogen peroxide (H₂O₂), jasmonic acid (JA), salicylic acid (SA) and other signal molecules have special chemical structures(Figure 1) and key effects. Together with other messengers such as calcium signaling system, they play a particularly prominent role". Please refer to lines 135-138 of the revised manuscript and change the track.

We changed" It was pointed out by the study that in plant cells, the activation effect of phenylalanine deaminase acting by endophytic bacterial inducers can be inhibited by catalase, and superoxide dismutase (SOD) can inhibit the promotion of secondary metabolite synthesis by inducers of antitoxin-like species" to " It is pointed out that in plant cells, catalase can inhibit the activation of phenylalanine deaminase by endophytic inducers, and superoxide dismutase (SOD) can inhibit the promotion of antitoxin inducers on the synthesis of secondary metabolites ". Please refer to lines 219-222 of the revised manuscript and change the track.

We changed" SA itself is converted to free radicals to undergo lipid peroxidation and enhances the signal through its peroxidation and a self-feedback mechanism of oxidation products with and SA, causing NPR1, TGA and WRKY, and other transcription factors to activate and interact [100], ultimately inducing PRs gene expression and allergic response, development of systemic acquired resistance and accumulation of secondary metabolites" to "SA enhances the signal through its own peroxidation and self-feedback mechanism of oxidation products. Intracellular signaling triggers the activation and interaction of transcription factors such as NPR1, TGA, and WRKY [101], which ultimately induce the expression of PRs genes and the development of allergic responses, leading to the development of acquired resistance and the accumulation of secondary metabolites in the host". Please refer to lines 255-260 of the revised manuscript and change the track.

We changed" It was pointed out by the study that in plant cells, the activation effect of phenylalanine deaminase acting by endophytic bacterial inducers can be inhibited by catalase, and superoxide dismutase (SOD) can inhibit the promotion of secondary metabolite synthesis by inducers of antitoxin-like species" to " It is pointed out that in plant cells, catalase can inhibit the activation of phenylalanine deaminase by endophytic inducers, and superoxide dismutase (SOD) can inhibit the promotion of antitoxin inducers on the synthesis of secondary metabolites ". Please refer to lines 219-222 of the revised manuscript and change the track.

We changed" Related studies revealed that NO may be located in the upstream position of the JA pathway, and NO-specific scavenger (cPTIO) and lipoxygenase inhibitor (NDGA) can inhibit the promotion of JA synthesis by Aspergillus niger cell wall inducers and the synthesis of plant secondary metabolites by NO, respectively " to " Related studies found that NO-specific scavengers (cPTIO) could inhibit the promotion of JA synthesis by Aspergillus niger cell wall inducers and lipoxygenase inhibitors (NDGA) could inhibit the effect of NO on the synthesis of plant secondary metabolites[103]. It is thus speculated that NO may be located in the upstream position of the JA pathway ". Please refer to lines 273-278 of the revised manuscript and change the track.

We changed" Therefore, it is necessary to systematically study the metabolic and regulatory pathways of specific endophytes within a large group of microorganisms to analyze the specific physiological patterns of plant responses to endophytes during the intercropping process and the differences in the intercropping between different taxa and host plants, to screen for more efficient endophytic species to further improve the quality of medicinal herbs " to " Therefore, it is necessary to conduct systematic studies on the metabolic pathways and regulatory pathways of specific endophytic bacteria within a large group of microorganisms. To further analyze the specific physiological patterns of plant responses to endophytes during the intercropping process. Through the differences in the interactions between different taxa and host plants, more efficient endophytic species can be selected to improve the quality of medicinal herbs ". Please refer to lines 353-359 of the revised manuscript and change the track.

 

Thank you very much for your attention and time. Look forward to hearing from you.

 

Sincerely yours,

Prof. Dr. Delin Xu

February 28, 2023

Reviewer 4 Report

Manuscript ID: processes-2233657

The paper entitled Signal molecules regulate the synthesis of secondary metabolites in the interaction between endophyte and medicinal plants. In this review, the authors reported the types and characteristics of the signaling molecules in the interactions between endophytic bacteria and medicinal plants. This is an interesting paper. However, for publication a minor revision is needed.

The paper would be easier to understand if the details of each table are explained and discussed (they should be more explained and detailed). However, table references must be cited in the text.

Specific comments:

1. Tables and figures should be cited in the text

2. Table 1: Names of strains should be in italic

3. Table 1: The name of the strain F5 should be added

4. Table 2: In the column of plant names (botany), the full scientific names must be added

5. Table 2: All scientific names should be in italic

6. Line 114: Tribulus Terrestris should be in italic

Line 170: The citations of these studies must be added

Lines 268, 270, 285 and 288: Names of species should be in italic (Aspergillus niger, A. chrysogenum, Penicillium citrinum and Taxus)

Author Response

Dear Reviewer，

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. We hope that our work can be improved again. Furthermore, we would like to show the details as follows:

 

Reviewer 4:

1. Tables and figures should be cited in the text.

Reply: Thank you for your kind advice. For your constructive comments, after careful examination, we have marked the reference positions of the figures and tables in the manuscript. The Figure 1 had been referred to line 137 of the revised version as its cited position of text, The Figure 2 had been referred to line 201 of the revised version as its cited position of text, The Figure 3 had been referred to line 240 of the revised version as its cited position of text, The Figure 4 had been referred to line 305 of the revised version as its cited position of text. The Table 1 had been referred to line 121 of the revised version as its cited position of text, The Table 2 had been referred to line 172 of the revised version as its cited position of text.

2.Table 1: Names of strains should be in italic.

Reply: Thank you for your kind suggestion. With regard to your constructive suggestions, we have improved the deficiencies of the manuscript by using italics for the names of strains involved in Table 1. Please refer to the "Strain (Genus)" column in Table 1 of the revised manuscript with track change.

3. Table 1: The name of the strain F5 should be added.

Reply: Thank you for your suggestion. We corrected the deficiencies of the manuscript, changing the name of strain "F5" to "Epichloë gansuensis". Please refer to the "Strain (Genus)" column in Table 1 of the revised manuscript with track changes.

4. Table 2: In the column of plant names (botany), the full scientific names must be added.

Reply: Thank you for your suggestion. We have revised the deficiencies and added the full scientific names of the plants involved in Table 2. Please refer to the "Botany" column in Table 2 of the revised manuscript with track changes.

5. Table 2: All scientific names should be in italic.

Reply: Thank you for your kind suggestion. After carefully reviewing the manuscript, we have used italics for the names of all scientific involved in Table 2. Please refer to the "Botany" column in Table 2 of the revised manuscript with track changes.

6. Line 114: Tribulus Terrestris should be in italic.

Reply: Thanks for your kind suggestions. We have changed "Tribulus Terrestris" to "Tribulus Terrestris". Please refer to lines 114-115 of the revised manuscript with track change.

7. Line 170: The citations of these studies must be added.

Reply: Thank you for your suggestion. We have added more appropriate citation "[52]Meng, X.; Xu, J.; He, Y.; Yang, K.Y.; Mordorski, B.; Liu, Y.; Zhang, S. Phosphorylation of an ERF transcription factor by Arabidopsis MPK3/MPK6 regulates plant defense gene induction and fungal resistance. Plant Cell. 2013, 25, 1126-1142" to our manuscript. Please refer to line 117, 527-528 of the revised manuscript with track change.

8. Lines 268, 270, 285 and 288: Names of species should be in italic (Aspergillus niger, A. chrysogenum, Penicillium citrinum and Taxus)

Reply: Thanks for your kind suggestions. We have modified "Aspergillus niger", "A. chrysogenum", "Penicillium citrinum" and "Taxus" to "Aspergillus niger", "A. chrysogenum", "Penicillium citrinum" and "Taxus". Please refer to lines 274, 278, 293, 296 of the revised manuscript with track change.

 

Thank you very much for your attention and time. Look forward to hearing from you.

 

Sincerely yours,

Prof. Dr. Delin Xu

Feburary 28, 2023

Reviewer 5 Report

The review article is very interesting and useful. I was happy to read it, the information in it was very helpful

 

Author Response

Dear Reviewer,

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. We hope that our work can be improved again. Furthermore, we would like to show the details as follows:

 

1. The review article is very interesting and useful. I was happy to read it, the information in it was very helpful.

Reply: Thank you for taking the time to review my manuscript and give me positive comments. We hope that after the revision, the information in this review article can provide you with helpful reference and we can get more recognition.

 

Thank you very much for your attention and time. Look forward to hearing from you.

 

Sincerely yours,

Prof. Dr. Delin Xu

February 28, 2023