Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Construction and Analysis of an Enzyme‐constrained Metabolic Model of Corynebacterium glutamicum

Jinhui Niu
,
Zhitao Mao
* ORCID logo ,
Yufeng Mao
,
Ke Wu
,
Zhenkun Shi
,
Qianqian Yuan
,
Jingyi Cai
,
Hongwu Ma
* ORCID logo
Version 1 : Received: 31 August 2022 / Approved: 1 September 2022 / Online: 1 September 2022 (09:54:55 CEST)

A peer-reviewed article of this Preprint also exists.

Niu, J.; Mao, Z.; Mao, Y.; Wu, K.; Shi, Z.; Yuan, Q.; Cai, J.; Ma, H. Construction and Analysis of an Enzyme-Constrained Metabolic Model of Corynebacterium glutamicum. Biomolecules 2022, 12, 1499. Niu, J.; Mao, Z.; Mao, Y.; Wu, K.; Shi, Z.; Yuan, Q.; Cai, J.; Ma, H. Construction and Analysis of an Enzyme-Constrained Metabolic Model of Corynebacterium glutamicum. Biomolecules 2022, 12, 1499.

Abstract

Genome-scale metabolic model (GEM) is a powerful tool for interpreting and predicting cellular phenotypes under various environmental and genetic perturbations. However, GEM only consid-ers stoichiometric constraints, and the simulated growth and product yield values will show a monotonic linear increase with increasing substrate uptake rate, which deviates from the experi-mentally measured values. Recently, the integration of enzymatic constraints into stoichiometry-based GEMs was proven to be effective in making novel discoveries and predicting new engineer-ing targets. Here we present the first genome-scale enzyme-constrained model (eciCW773) for Corynebacterium glutamicum reconstructed by integrating enzyme kinetic data from various sources using ECMpy workflow based on the high-quality GEM of C. glutamicum (obtained by modifying the iCW773 model). The enzyme-constrained model improved the prediction of pheno-types and simulated overflow metabolism, while also recapitulating the trade-off between biomass yield and enzyme usage efficiency. Finally, we used eciCW773 to identify several gene modifica-tion targets for L-lysine production, most of which agree with previously reported genes. This study shows that incorporating enzyme kinetic information into the GEM enhances the cellular phenotypes prediction of C. glutamicum, which can help identify key enzymes and thus provide reliable guidance for metabolic engineering.

Keywords

enzyme-constrained model; Corynebacterium glutamicum; metabolic engineering

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (2)

Comment 1
Received: 21 September 2022
The commenter has declared there is no conflict of interests.
Comment: Glad to see that the research on the Cornybacterium glutamicum is continuing. I was wondering if you are aware of the most recent GEM of the Corynebacterium glutamicum:
https://www.frontiersin.org/articles/10.3389/fmicb.2021.750206/full
This publication also includes valuable comments on the GEM you used for your ec-model.
+ Respond to this comment
Response 1 to Comment 1
Received: 15 October 2022
Commenter:
Zhitao Mao

The commenter has declared there is no conflict of interests.
Comment: Although the iCGB21FR model is the most recent model for Corynebacterium glutamicum, we found some problems with the model that can have an impact on simulation predictions. The main points include the following:
(1) There are other carbon sources other than glucose inside the medium, such as catechuic acid, urea, and biotin.
(2) The reason for the better growth rate predicted by the model is that the upper bound for all components of the medium is 10, including the oxygen supply reaction, the hydrogen exchange reaction, and the NH4 exchange reaction. If the upper bound for the oxygen/hydrogen/NH4 exchange reaction is set to 1000, the growth rate is 1.84, which is much greater than the experimental value.
(3) Corynebacterium glutamicum ATCC13032 is biotin-deficient, and the simulation results show that the growth simulated by the model is not affected without supplying biotin (EX_btn_e), compared to iCW773 which can simulate a growth rate of 0 in this case.
For the above reasons, we chose to construct the enzyme-constrained model based on the iCW773 model.

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 2
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.