ArticlePLoS biology2005
Flux analysis uncovers key role of functional redundancy in formaldehyde metabolism.
Article in PLoS biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
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- Genome-scale flux balance analysis reveals redox trade-offs in the metabolism of the thermoacidophileFrontiers in systems biology · 2024Article
- Tailored extraction and ion mobility-mass spectrometry enables isotopologue analysis of tetrahydrofolate vitamers.Analytical and bioanalytical chemistry · 2023Article
- Asparagine Uptake: a Cellular Strategy ofApplied and environmental microbiology · 2023Article
- Compartment-related aspects of XoxF protein functionality in Methylorubrum extorquens DM4 analysed using its cytoplasmic targeting.Antonie van Leeuwenhoek · 2023Article
- Aerobic Methoxydotrophy: Growth on Methoxylated Aromatic Compounds byFrontiers in microbiology · 2022Article
- Verrucomicrobial methanotrophs: ecophysiology of metabolically versatile acidophiles.FEMS microbiology reviews · 2021Review
- Genetic Context Significantly Influences the Maintenance and Evolution of Degenerate Pathways.Genome biology and evolution · 2021Article
- EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.PLoS biology · 2021Article
- Formaldehyde-responsive proteins, TtmR and EfgA, reveal a tradeoff between formaldehyde resistance and efficient transition to methylotrophy inJournal of bacteriology · 2021Article
- Global Transcriptional Response ofMicroorganisms · 2021Article
- Carbon Assimilation Strategies in Ultrabasic Groundwater: Clues from the Integrated Study of a Serpentinization-Influenced Aquifer.mSystems · 2020Article
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- Continuous Culture Adaptation ofFrontiers in microbiology · 2019Article
- Hopanoid-free Methylobacterium extorquens DM4 overproduces carotenoids and has widespread growth impairment.PloS one · 2017Article
- Transfer of a Catabolic Pathway for Chloromethane in Methylobacterium Strains Highlights Different Limitations for Growth with Chloromethane or with Dichloromethane.Frontiers in microbiology · 2016Article
- Marker Exchange Mutagenesis of mxaF, Encoding the Large Subunit of the Mxa Methanol Dehydrogenase, in Methylosinus trichosporium OB3b.Applied and environmental microbiology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14)C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.