Longevity of major coenzymes allows minimal de novo synthesis in microorganisms

Nature Microbiology
Johannes HartlJulia A Vorholt

Abstract

Coenzymes are vital for cellular metabolism and act on the full spectrum of enzymatic reactions. Intrinsic chemical reactivity, enzyme promiscuity and high flux through their catalytic cycles make coenzymes prone to damage. To counteract such compromising factors and ensure stable levels of functional coenzymes, cells use a complex interplay between de novo synthesis, salvage, repair and degradation. However, the relative contribution of these factors is currently unknown, as is the overall stability of coenzymes in the cell. Here, we use dynamic 13C-labelling experiments to determine the half-life of major coenzymes of Escherichia coli. We find that coenzymes such as pyridoxal 5-phosphate, flavins, nicotinamide adenine dinucleotide (phosphate) and coenzyme A are remarkably stable in vivo and allow biosynthesis close to the minimal necessary rate. In consequence, they are essentially produced to compensate for dilution by growth and passed on over generations of cells. Exceptions are antioxidants, which are short-lived, suggesting an inherent requirement for increased renewal. Although the growth-driven turnover of stable coenzymes is apparently subject to highly efficient end-product homeostasis, we exemplify that coenzyme poo...Continue Reading

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Citations

Jun 28, 2017·Nature Microbiology·Jens Nielsen
Aug 12, 2018·The FEBS Journal·Julia Becker-KetternCarole L Linster
May 28, 2019·Frontiers in Molecular Biosciences·Björn RichtsFabian M Commichau
Nov 7, 2019·Metabolites·Daqiang PanBernd Kammerer
Feb 25, 2020·Nature Metabolism·Johannes HartlJulia A Vorholt
Jan 10, 2021·Nature Communications·Vitor MendesTom L Blundell
Oct 1, 2018·Current Opinion in Chemical Biology·Valérie de Crécy-LagardAndrew D Hanson

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