Preview

Vavilov Journal of Genetics and Breeding

Advanced search

A software module to assess the metabolic potential of mutant strains of the bacterium Corynebacterium glutamicum

https://doi.org/10.18699/vjgb-24-97

Abstract

Technologies for the production of a range of compounds using microorganisms are becoming increas­ingly popular in industry. The creation of highly productive strains whose metabolism is aimed to the synthesis of a specific desired product is impossible without complex directed modifications of the genome using mathematical and computer modeling methods. One of the bacterial species actively used in biotechnological production is Co­rynebacterium glutamicum. There are already 5 whole-genome flux balance models for it, which can be used for me­tabolism research and optimization tasks. The paper presents fluxMicrobiotech, a software module developed at the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, which implements a se­ries of computational protocols designed for high-performance computer analysis of C. glutamicum whole-genome flux balance models. The tool is based on libraries from the opencobra community (https://opencobra.github.io) within the Python programming language (https://www.python.org), using the Pandas (https://pandas.pydata.org) and Escher (https://escher.readthedocs.io) libraries . It is configured to operate on a ‘file-in/file-out’ basis. The model, environmental conditions, and model constraints are specified as separate text table files, which allows one to pre­pare a series of files for each section, creating databases of available test scenarios for variations of the model. Or vice versa, allowing a single model to be tested under a series of different cultivation conditions. Post-processing tools for modeling data are set up, providing visualization of summary charts and metabolic maps.

About the Authors

F. V. Kazantsev
Kurchatov Genomic Center of ICG SB RAS; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University
Russian Federation

Novosibirsk



M. F. Trofimova
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation

Novosibirsk



T. M. Khlebodarova
Kurchatov Genomic Center of ICG SB RAS; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation

Novosibirsk



Yu. G. Matushkin
Kurchatov Genomic Center of ICG SB RAS; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University
Russian Federation

Novosibirsk



S. A. Lashin
Kurchatov Genomic Center of ICG SB RAS; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University
Russian Federation

Novosibirsk



References

1. Ananda R., Daud K.M., Zainudin S. A review of advances in integrating gene regulatory networks and metabolic networks for designing strain optimization. J. King Saud Univ. Comput. Inf. Sci. 2024; 36(6):102120. doi 10.1016/j.jksuci.2024.102120

2. Barcelos M.C.S., Lupki F.B., Campolina G.A., Nelson D.L., Molina G. The colors of biotechnology: general overview and developments of white, green and blue areas. FEMS Microbiol. Lett. 2018;365(21): fny239. doi 10.1093/femsle/fny239

3. Feierabend M., Renz A., Zelle E., Nöh K., Wiechert W., Dräger A. High-quality genome-scale reconstruction of Corynebacterium glutamicum ATCC 13032. Front. Microbiol. 2021;12:750206. doi 10.3389/fmicb.2021.750206

4. Gu C., Kim G.B., Kim W.J., Kim H.U., Lee S.Y. Current status and applications of genome-scale metabolic models. Genome Biol. 2019; 20(1):121. doi 10.1186/s13059-019-1730-3

5. Herrmann H.A., Dyson B.C., Vass L., Johnson G.N., Schwartz J.-M. Flux sampling is a powerful tool to study metabolism under changing environmental conditions. NPJ Syst. Biol. Appl. 2019;5(1):32. doi 10.1038/s41540-019-0109-0

6. Jensen P.R., Michelsen O., Westerhoff H.V. Control analysis of the dependence of Escherichia coli physiology on the H+-ATPase. Proc. Natl. Acad. Sci. USA. 1993;90(17):8068-8072. doi 10.1073/pnas.90.17.8068

7. King Z.A., Dräger A., Ebrahim A., Sonnenschein N., Lewis N.E., Palsson B.O. Escher: a web application for building, sharing, and embedding data-rich visualizations of biological pathways. PLoS Comput. Biol. 2015;11(8):e1004321. doi 10.1371/journal.pcbi.1004321

8. Kinoshita S., Udaka S., Shimono M. Studies on the amino acid fermentation. J. Gen. Appl. Microbiol. 1957;3(3):193-205. doi 10.2323/jgam.3.193

9. Kjeldsen K.R., Nielsen J. In silico genome-scale reconstruction and validation of the Corynebacterium glutamicum metabolic network. Biotechnol. Bioeng. 2009;102(2):583-597. doi 10.1002/bit.22067

10. Kulyashov M.A., Kolmykov S.K., Khlebodarova T.M., Akberdin I.R. State-of the-art constraint-based modeling of microbial metabolism: from basics to context-specific models with a focus on methanotrophs. Microorganisms. 2023;11(12):2987. doi 10.3390/microorganisms11122987

11. Machado D., Andrejev S., Tramontano M., Patil K.R. Fast automated reconstruction of genome-scale metabolic models for microbial species and communities. Nucleic Acids Res. 2018;46(15):7542-7553. doi 10.1093/nar/gky537

12. Mao Z., Yuan Q., Li H., Zhang Y., Huang Y., Yang C., Wang R., Yang Y., Wu Y., Yang S., Liao X., Ma H. CAVE: a cloud-based platform for analysis and visualization of metabolic pathways. Nucleic Acids Res. 2023;51(W1):W70-W77. doi 10.1093/nar/gkad360

13. Mei J., Xu N., Ye C., Liu L., Wu J. Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114. Gene. 2016;575(2):615-622. doi 10.1016/j.gene.2015.09.038

14. Mendoza S.N., Olivier B.G., Molenaar D., Teusink B. A systematic assessment of current genome-scale metabolic reconstruction tools. Genome Biol. 2019;20(1):158. doi 10.1186/s13059-019-1769-1

15. 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(10):1499. doi 10.3390/biom12101499

16. Norsigian C.J., Pusarla N., McConn J.L., Yurkovich J.T., Dräger A., Palsson B.O., King Z. BiGG Models 2020: multi-strain genomescale models and expansion across the phylogenetic tree. Nucleic Acids Res. 2019;48(D1):D402-D406. doi 10.1093/nar/gkz1054

17. Sheremetieva M.E., Anufriev K.E., Khlebodarova T.M., Kolchanov N.A., Yanenko A.S. Rational metabolic engineering of Corynebacterium glutamicum to create a producer of L-valine. Vavilov J. Genet. Breed. 2023;26(8):743-757. doi 10.18699/VJGB-22-90

18. Sheremetieva M.E., Khlebodarova T.M., Derbikov D.D., Rozantseva V.V., Kolchanov N.A., Yanenko A.S. Systems metabolic engineering of Corynebacterium glutamicum to create a producer of L-valine. Biotekhnologiya = Biotechnology. 2024;40(3):3-23. doi 10.56304/S0234275824030025 (in Russian)

19. Tsuge Y., Matsuzawa H. Recent progress in production of amino acid‐derived chemicals using Corynebacterium glutamicum. World J. Microbiol. Biotechnol. 2021;37(3):49. doi 10.1007/s11274-021-03007-4

20. Wendisch V.F., Jorge J.M.P., Pérez-García F., Sgobba E. Updates on industrial production of amino acids using Corynebacterium glutamicum. World J. Microbiol. Biotechnol. 2016;32(6):105. doi 10.1007/s11274-016-2060-1

21. Zelle E., Nööh K., Wiechert W. Growth and production capabilities of Corynebacterium glutamicum: interrogating a genome-scale metabolic network model. In: Burkovski A. (Ed.) Corynebacterium glutamicum: From Systems Biology to Biotechnological Applications. Caister Acad. Press, 2015;39-56. doi 10.21775/9781910190050.04

22. Zhang Yu, Cai J., Shang X., Wang B., Liu S., Chai X., Tan T., Zhang Yun, Wen T. A new genome-scale metabolic model of Corynebacterium glutamicum and its application. Biotechnol. Biofuels. 2017;10(1):169. doi 10.1186/s13068-017-0856-3


Review

Views: 200


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2500-3259 (Online)