Longevity of major coenzymes allows minimal de novo synthesis in microorganisms

• Published in: Nature microbiology Vol. 2; no. 7; p. 17073
• Main Authors: Hartl, Johannes, Kiefer, Patrick, Meyer, Fabian, Vorholt, Julia A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.05.2017; Nature Publishing Group
• Subjects: 631/326/41/1969; 631/326/41/2095; 631/45/320; Antioxidants; Bacillus subtilis - metabolism; Biodegradation; Biomedical and Life Sciences; Carbon Isotopes - metabolism; Coenzyme A; Coenzymes; Coenzymes - metabolism; Escherichia coli - metabolism; Flavin; Half-Life; Homeostasis; Infectious Diseases; Isotope Labeling; Labeling; Life Sciences; Longevity; Medical Microbiology; Microbiology; NADPH; Nicotinamide; Nutrient requirements; Parasitology; Saccharomyces cerevisiae - metabolism; Staining and Labeling; Virology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/nmicrobiol.2017.73

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 13 C-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 pools are propagated in excess in relation to actual growth requirements. Additional testing of Bacillus subtilis and Saccharomyces cerevisiae suggests that coenzyme longevity is a conserved feature in biology. Metabolomics analyses of Escherichia coli , Bacillus subtilis and Saccharomyces cerevisiae show that, unlike other metabolites, coenzymes such as pyridoxal 5'-phosphate, NAD(P), coenzyme A and flavins are long-lived in vivo and passed on over generations.