The Application of Corynebacterium glutamicum in l-Threonine Biosynthesis

Round 1

Reviewer 1 Report

In this review article by Duan et al., the history and recent advances in threonine production by Corynebacterium glutamicum are well documented. Especially, the authors focused on the biosynthetic pathway of threonine and metabolic engineering technology to improve threonine production.

Comments:

1)     Threonine producer strains have been developed mainly using Escherichia coli as well as Corynebacterium glutamicum. Regulatory networks of threonine biosynthetic pathways are different between these two microorganisms. The advantages and disadvantages of C. glutamicum should be discussed from this point of view.

2)     Lines 246, 262, 283, 288, and 291. The term "exocytosis" is not suitable for this review because this term is usually used for the secretory vesicle-dependent export system.

3)     Unfortunately, there are so many mistakes in the manuscript. The manuscript should be checked by a professional editor. For example; "Corynebacterium glutamicum" should be written as "C. glutamicum" (lines 113, 115, 121, 125, and so on). Gene names and organism names should be italicized. For example, "lysC" should be italicized (line 205). "the" should not be italicized (line 234).

4)     The references do not follow the journal's style.

Author Response

Dear Editors and Reviewers:

Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “The Application of Corynebacterium Glutamicum in L-threonine Biosynthesis” (ID: fermentation-2559427). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in yellow in the manuscript. The corrections in the paper and the responds to the reviewer’s comments are as flowing:

Comment 1):

Threonine producer strains have been developed mainly using Escherichia coli as well as Corynebacterium glutamicum. Regulatory networks of threonine biosynthetic pathways are different between these two microorganisms. The advantages and disadvantages of C. glutamicum should be discussed from this point of view.

Response to comment:

The content of Escherichia coli has been deleted from the manuscript. This manuscript mainly discusses Corynebacterium glutamicum.

Comment 2):

Lines 246, 262, 283, 288, and 291. The term "exocytosis" is not suitable for this review because this term is usually used for the secretory vesicle-dependent export system.

Response to comment:

The word "exocytosis" has been replaced by "exporter" in this manuscript.

Comment 3):

Unfortunately, there are so many mistakes in the manuscript. The manuscript should be checked by a professional editor. For example; "Corynebacterium glutamicum" should be written as "C. glutamicum" (lines 113, 115, 121, 125, and so on). Gene names and organism names should be italicized. For example, "lysC" should be italicized (line 205). "the" should not be italicized (line 234).

Response to comment:

The abbreviation for "Corynebacterium glutamicum" has been corrected. Gene names and organism names have been italicized.

Comment 4):

The references do not follow the journal's style.

Response to comment:

The references have been changed.

We appreciate for Reviewer’s warm work earnestly, and hope that the correction will meet with approval.

Once again, thank you very much for your comments and suggestions.

Best regards,

Deqiang Zhu

Reviewer 2 Report

This is a sound review on the biosynthesis of L-threonine in Corynebacterium glutamicum. Usually a review is written if there is an exciting new development in the field. Though considerable progress in the biotechnology of the production of L-threonine has been made, no breakthrough has been visible. Therefore, the reader asks why this review is a necessary contribution to biotechnology.

“Threonine has four stereoisomers, of which L-threonine is naturally occurring and exerts physiological effects on the body.” Perhaps the reader will know the other stereoisomers. The four stereoisomers have the following configurations: (2S,3R) L-threonine, (2R,3S ) D-threonine, (2S,3S)  L-allothreonine and (2R,3R) D-allothreonine.

The yields of L-threonine under various conditions are given as g/L or in mM. For comparative reasons the authors should give the yields always as g/L or preferentially as mM. To give the concentrations as 10.0 mM fakes an accuracy which has not been achieved, write 10 mM, 30 mM and 100 mM L-threonine.

What do you mean by “strengthening the genes”?

Author Response

Dear Editors and Reviewers:

Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “The Application of Corynebacterium Glutamicum in L-threonine Biosynthesis” (ID: fermentation-2559427). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in yellow in the manuscript. The corrections in the paper and the responds to the reviewer’s comments are as flowing:

Comment 1):

This is a sound review on the biosynthesis of L-threonine in Corynebacterium glutamicum. Usually a review is written if there is an exciting new development in the field. Though considerable progress in the biotechnology of the production of L-threonine has been made, no breakthrough has been visible. Therefore, the reader asks why this review is a necessary contribution to biotechnology.

Response to comment:

At present, the synthesis of L-threonine using Corynebacterium glutamicum is still in the relatively initial research stage, and there is no large-scale production of L-threonine using C. glutamicum. This paper provides a systematic review of the latest research on the production of threonine by C. glutamicum and aims to help readers understand the latest research progress in the production of L-threonine using C. glutamicum. Therefore, we believe this paper is useful for readers is interested on the use of metabolic engineering technology to improve the production of L-threonine.

Comment 2):

“Threonine has four stereoisomers, of which L-threonine is naturally occurring and exerts physiological effects on the body.” Perhaps the reader will know the other stereoisomers. The four stereoisomers have the following configurations: (2S,3R) L-threonine, (2R,3S) D-threonine, (2S,3S) L-allothreonine and (2R,3R) D-allothreonine.

Response to comment:

Considering the Reviewer’s suggestion, we have deleted the expression of stereoisomers, because this paper only refer to threonine of L-configuration.

Comment 3):

The yields of L-threonine under various conditions are given as g/L or in mM. For comparative reasons the authors should give the yields always as g/L or preferentially as mM. To give the concentrations as 10.0 mM fakes an accuracy which has not been achieved, write 10 mM, 30 mM and 100 mM L-threonine.

Response to comment:

It is really true as Reviewer suggested that the yields should be given yields always as g/L or preferentially as mM. Therefore, the unit has been unified in the manuscript.

Comment 4):

What do you mean by “strengthening the genes”?

Response to comment:

“Strengthening the genes” means that strengthening the expression of the target genes encoding the key enzymes.

We appreciate for Reviewer’s warm work earnestly, and hope that the correction will meet with approval.

Once again, thank you very much for your comments and suggestions.

Best regards,

Deqiang Zhu