NDLI: Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms

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Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms

Content Provider	MDPI
Author	Chung, Carolina H. Lin, Da-Wei Eames, Alec Chandrasekaran, Sriram
Copyright Year	2021
Description	Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions. This limitation of GEMs has prompted the development of new methods to integrate regulatory mechanisms, thereby enhancing the predictive capabilities and broadening the scope of GEMs. Here, we cover integrative models encompassing six types of regulatory mechanisms: transcriptional regulatory networks (TRNs), post-translational modifications (PTMs), epigenetics, protein–protein interactions and protein stability (PPIs/PS), allostery, and signaling networks. We discuss 22 integrative GEM modeling methods and how these have been used to simulate metabolic regulation during normal and pathological conditions. While these advances have been remarkable, there remains a need for comprehensive and widespread integration of regulatory constraints into GEMs. We conclude by discussing challenges in constructing GEMs with regulation and highlight areas that need to be addressed for the successful modeling of metabolic regulation. Next-generation integrative GEMs that incorporate multiple regulatory mechanisms and their crosstalk will be invaluable for discovering cell-type and disease-specific metabolic control mechanisms.
Starting Page	606
e-ISSN	22181989
DOI	10.3390/metabo11090606
Journal	Metabolites
Issue Number	9
Volume Number	11
Language	English
Publisher	MDPI
Publisher Date	2021-09-07
Access Restriction	Open
Subject Keyword	Metabolites Cell Biology Metabolic Regulation Metabolic Networks Constraint-based Modeling Systems Biology Genome-scale Network Models
Content Type	Text
Resource Type	Article

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