Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges
This review is a part of the SI ‘Genome-Scale Modeling of Microorganisms in the Real World’. The goal of GEM is the accurate prediction of the phenotype from its respective genotype under specified environmental conditions. This review focuses on the dynamic phenotype; prediction of the real-life be...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/9/11/2352 |
| _version_ | 1797509272867700736 |
|---|---|
| author | Nicolai S. Panikov |
| author_facet | Nicolai S. Panikov |
| author_sort | Nicolai S. Panikov |
| collection | DOAJ |
| description | This review is a part of the SI ‘Genome-Scale Modeling of Microorganisms in the Real World’. The goal of GEM is the accurate prediction of the phenotype from its respective genotype under specified environmental conditions. This review focuses on the dynamic phenotype; prediction of the real-life behaviors of microorganisms, such as cell proliferation, dormancy, and mortality; balanced and unbalanced growth; steady-state and transient processes; primary and secondary metabolism; stress responses; etc. Constraint-based metabolic reconstructions were successfully started two decades ago as FBA, followed by more advanced models, but this review starts from the earlier nongenomic predecessors to show that some GEMs inherited the outdated biokinetic frameworks compromising their performances. The most essential deficiencies are: (i) an inadequate account of environmental conditions, such as various degrees of nutrients limitation and other factors shaping phenotypes; (ii) a failure to simulate the adaptive changes of MMCC (MacroMolecular Cell Composition) in response to the fluctuating environment; (iii) the misinterpretation of the SGR (Specific Growth Rate) as either a fixed constant parameter of the model or independent factor affecting the conditional expression of macromolecules; (iv) neglecting stress resistance as an important objective function; and (v) inefficient experimental verification of GEM against simple growth (constant MMCC and SGR) data. Finally, we propose several ways to improve GEMs, such as replacing the outdated Monod equation with the SCM (Synthetic Chemostat Model) that establishes the quantitative relationships between primary and secondary metabolism, growth rate and stress resistance, process kinetics, and cell composition. |
| first_indexed | 2024-03-10T05:15:22Z |
| format | Article |
| id | doaj.art-fd4e41c8b5ae486da7685dc7683d79ac |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T05:15:22Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-fd4e41c8b5ae486da7685dc7683d79ac2023-11-23T00:30:09ZengMDPI AGMicroorganisms2076-26072021-11-01911235210.3390/microorganisms9112352Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and ChallengesNicolai S. Panikov0Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USAThis review is a part of the SI ‘Genome-Scale Modeling of Microorganisms in the Real World’. The goal of GEM is the accurate prediction of the phenotype from its respective genotype under specified environmental conditions. This review focuses on the dynamic phenotype; prediction of the real-life behaviors of microorganisms, such as cell proliferation, dormancy, and mortality; balanced and unbalanced growth; steady-state and transient processes; primary and secondary metabolism; stress responses; etc. Constraint-based metabolic reconstructions were successfully started two decades ago as FBA, followed by more advanced models, but this review starts from the earlier nongenomic predecessors to show that some GEMs inherited the outdated biokinetic frameworks compromising their performances. The most essential deficiencies are: (i) an inadequate account of environmental conditions, such as various degrees of nutrients limitation and other factors shaping phenotypes; (ii) a failure to simulate the adaptive changes of MMCC (MacroMolecular Cell Composition) in response to the fluctuating environment; (iii) the misinterpretation of the SGR (Specific Growth Rate) as either a fixed constant parameter of the model or independent factor affecting the conditional expression of macromolecules; (iv) neglecting stress resistance as an important objective function; and (v) inefficient experimental verification of GEM against simple growth (constant MMCC and SGR) data. Finally, we propose several ways to improve GEMs, such as replacing the outdated Monod equation with the SCM (Synthetic Chemostat Model) that establishes the quantitative relationships between primary and secondary metabolism, growth rate and stress resistance, process kinetics, and cell composition.https://www.mdpi.com/2076-2607/9/11/2352growth kineticssurvivaldeathsubstrate limitationstarvationgene expression |
| spellingShingle | Nicolai S. Panikov Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges Microorganisms growth kinetics survival death substrate limitation starvation gene expression |
| title | Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges |
| title_full | Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges |
| title_fullStr | Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges |
| title_full_unstemmed | Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges |
| title_short | Genome-Scale Reconstruction of Microbial Dynamic Phenotype: Successes and Challenges |
| title_sort | genome scale reconstruction of microbial dynamic phenotype successes and challenges |
| topic | growth kinetics survival death substrate limitation starvation gene expression |
| url | https://www.mdpi.com/2076-2607/9/11/2352 |
| work_keys_str_mv | AT nicolaispanikov genomescalereconstructionofmicrobialdynamicphenotypesuccessesandchallenges |