Primordial‐like enzymes from bacteria with reduced genomes

• Published in: Molecular microbiology 2017-08, Vol.105 (4), p.508-524
• Main Authors: Ferla, Matteo P., Brewster, Jodi L., Hall, Kelsi R., Evans, Gary B., Patrick, Wayne M.
• Format: Article
• Language: English
• Subjects: Abundance; Alanine; Alanine - metabolism; Alanine racemase; Amino Acid Sequence; Bacteria; Catalytic Domain; Chemical reactions; E coli; Enzymes; Enzymes - genetics; Escherichia coli - genetics; Fruit flies; Genome - genetics; Genome, Bacterial - genetics; Genomes; Lyases - genetics; Lyases - metabolism; Metabolic networks; Metabolic Networks and Pathways; Microorganisms; Streamlining; Textbooks; Thermotoga maritima - genetics; Wolbachia - genetics
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.13737

Summary The first cells probably possessed rudimentary metabolic networks, built using a handful of multifunctional enzymes. The promiscuous activities of modern enzymes are often assumed to be relics of this primordial era; however, by definition these activities are no longer physiological. There are many fewer examples of enzymes using a single active site to catalyze multiple physiologically‐relevant reactions. Previously, we characterized the promiscuous alanine racemase (ALR) activity of Escherichia coli cystathionine β‐lyase (CBL). Now we have discovered that several bacteria with reduced genomes lack alr, but contain metC (encoding CBL). We characterized the CBL enzymes from three of these: Pelagibacter ubique, the Wolbachia endosymbiont of Drosophila melanogaster (wMel) and Thermotoga maritima. Each is a multifunctional CBL/ALR. However, we also show that CBL activity is no longer required in these bacteria. Instead, the wMel and T. maritima enzymes are physiologically bi‐functional alanine/glutamate racemases. They are not highly active, but they are clearly sufficient. Given the abundance of the microorganisms using them, we suggest that much of the planet's biochemistry is carried out by enzymes that are quite different from the highly‐active exemplars usually found in textbooks. Instead, primordial‐like enzymes may be an essential part of the adaptive strategy associated with streamlining. Enzymes speed up the rates of chemical reactions inside every cell of every organism. The textbook view is that they have evolved to be highly active and highly specific. We show that some of the most abundant organisms on the planet – bacteria from the ocean, and others that infect insects – instead use enzymes that are weakly active and multifunctional, and therefore, resemble those that existed in the primordial soup.