Convergent evolution of a modified, acetate-driven TCA cycle in bacteria

Abstract

The tricarboxylic acid (TCA) cycle is central to energy production and biosynthetic precursor synthesis in aerobic organisms. There exist few known variations of a complete TCA cycle, with the common notion being that the enzymes involved have already evolved towards optimal performance. Here, we present evidence that an alternative TCA cycle, in which acetate:succinate CoA-transferase (ASCT) replaces the enzymatic step typically performed by succinyl-CoA synthetase (SCS), has arisen in diverse bacterial groups, including microbial symbionts of animals such as humans and insects.Keywords citric acid cycle; Krebs cycle; acetate; gut microbiota; Snodgrassella alvi Main textThe tricarboxylic acid (TCA) cycle arose during early evolution and represents a core process in aerobic respiration and production of carbon-based precursor molecules needed for the biosynthesis of amino acids, nucleotides and cofactors. The enzymes that complete the cycle show homology across Bacteria, Archaea, and Eukaryota, and are highly efficient 1,2 ; consequently, there are relatively few known variations of a complete TCA cycle. Many bacteria have incomplete cycles, while some autotrophs use a reverse (reductive) cycle to fix carbon from CO 2 3 . Alternative oxidative cycles have been proposed to operate in Cyanobacteria 4 , Mycobacterium 5 , and Helicobacter 6 . Another variant cycle was identified in Acetobacter aceti, whereby succinyl-CoA is converted to succinate by an acetate:succinate CoA-transferase (ASCT) instead of the typical succinyl-CoA synthetase Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Gut microbial functional maturation and succession during human early life

“…Rather, our metaproteomics data suggested that taxa within Firmicutes and to a minor extent in Bacteroidetes, Proteobacteria and Verrumicrobia employed a variation of the classical TCA cycle based on an unorthodox enzyme, acetate:succinate CoAtransferase (ASCT) to synthesize succinyl-CoA. Kwong et al recently showed that ASCT genes were widespread in prokaryotic genomes and functionally replaced SCS in TCA cycle of human microbial commensals (Kwong et al, 2017). In a carbon-rich anaerobic gut ecosystem, this strategy may be a result of niche specialization where gut microbiota may use acetyl-CoA, the keystone molecule of central metabolism produced from monosaccharides, amino acids, fatty acids and other secondary metabolites, as driver of a reverse TCA cycle to maintain redox balance and obtain energy for growth.…”

“…Kwong et al . recently showed that ASCT genes were widespread in prokaryotic genomes and functionally replaced SCS in TCA cycle of human microbial commensals (Kwong et al ., ). In a carbon‐rich anaerobic gut ecosystem, this strategy may be a result of niche specialization where gut microbiota may use acetyl‐CoA, the keystone molecule of central metabolism produced from monosaccharides, amino acids, fatty acids and other secondary metabolites, as driver of a reverse TCA cycle to maintain redox balance and obtain energy for growth.…”

Functional roles and metabolic niches in the honey bee gut microbiota

“…How bacterial activities in the bee gut impact the host or gut environment has so far remained elusive except for a few cases. For example, the microaerophilic core member S. alvi has been implicated in maintaining anoxic conditions in the ileum [18] by respiring oxygen via an alternative citrate cycle driven by acetate [23,53,54]. Interestingly, acetate is one of the major fermentation products generated by G. apicola, which together with S. alvi forms a multispecies biofilm on top of the host epithelium, from where the oxygen may be released.…”

On the role of the tricarboxylic acid cycle in plant productivity

“…In addition to the variation within the individual reactions, per se , there are other variations of note, not least of which being the Anon‐Buchanan cycle, in which the TCA cycle runs in the reverse direction in a wide range of bacteria (Buchanan et al ). There are also a range of shunts and bypasses which occur in non‐plant systems, including the citramalate shunt (Filatova et al ), the bypass of the 2‐oxoglutarate dehydrogenase reaction uncovered recently in cyanobacteria (Zhang and Bryant ; Steinhauser et al ), and the recently described acetate shunt (Kwong et al ), as well as variants of the glycoxylate shunt (Vuoristo et al ) which is confined to specialized peroxisomes, known as glycoxysomes in plants and absent in mammals. A maleate shunt has also been described in several bacteria and the compound is detectable in plants and correlates with levels of malate and fumarate, yet the genes/enzymes responsible have not yet been characterized in plants (Sweetlove et al ; Sweetlove et al ).…”