Early evolution of the biotin-dependent carboxylase family

Abstract

BackgroundBiotin-dependent carboxylases are a diverse family of carboxylating enzymes widespread in the three domains of life, and thus thought to be very ancient. This family includes enzymes that carboxylate acetyl-CoA, propionyl-CoA, methylcrotonyl-CoA, geranyl-CoA, acyl-CoA, pyruvate and urea. They share a common catalytic mechanism involving a biotin carboxylase domain, which fixes a CO2 molecule on a biotin carboxyl carrier peptide, and a carboxyl transferase domain, which transfers the CO2 moiety to the specific substrate of each enzyme. Despite this overall similarity, biotin-dependent carboxylases from the three domains of life carrying their reaction on different substrates adopt very diverse protein domain arrangements. This has made difficult the resolution of their evolutionary history up to now.ResultsTaking advantage of the availability of a large amount of genomic data, we have carried out phylogenomic analyses to get new insights on the ancient evolution of the biotin-dependent carboxylases. This allowed us to infer the set of enzymes present in the last common ancestor of each domain of life and in the last common ancestor of all living organisms (the cenancestor). Our results suggest that the last common archaeal ancestor had two biotin-dependent carboxylases, whereas the last common bacterial ancestor had three. One of these biotin-dependent carboxylases ancestral to Bacteria most likely belonged to a large family, the CoA-bearing-substrate carboxylases, that we define here according to protein domain composition and phylogenetic analysis. Eukaryotes most likely acquired their biotin-dependent carboxylases through the mitochondrial and plastid endosymbioses as well as from other unknown bacterial donors. Finally, phylogenetic analyses support previous suggestions about the existence of an ancient bifunctional biotin-protein ligase bound to a regulatory transcription factor.ConclusionsThe most parsimonious scenario for the early evolution of the biotin-dependent carboxylases, supported by the study of protein domain composition and phylogenomic analyses, entails that the cenancestor possessed two different carboxylases able to carry out the specific carboxylation of pyruvate and the non-specific carboxylation of several CoA-bearing substrates, respectively. These enzymes may have been able to participate in very diverse metabolic pathways in the cenancestor, such as in ancestral versions of fatty acid biosynthesis, anaplerosis, gluconeogenesis and the autotrophic fixation of CO2.

OPINIONS Acetyl-coenzyme A carboxylase – an attractive enzyme for biotechnology

“…3). The prokaryotic and eukaryotic types of ACCases are evolutionary related and the phylogeny of the modules provides some hints about their cenancestor, a split between Archaea and Bacteria, and arising of Eukaryota (Lombard and Moreira, 2011).…”

“…3). The prokaryotic and eukaryotic types of ACCases are evolutionary related and the phylogeny of the modules provides some hints about their cenancestor, a split between Archaea and Bacteria, and arising of Eukaryota (Lombard and Moreira, 2011).Phylogeny is out of scope of this manuscript, but acetyl-coenzyme A carboxylases from various organisms representing various domains of life are discussed in this review. While, traditionally two abbreviations are in use for acetyl-coenzyme A carboxylase: ACCase for plant enzymes and ACC for human (metazoan) ones, combining them (often in the same paragraph or even sentence) may be confusing.…”

The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

“…Phylogenetic analyses of the carboxyltransferase domains of bacterial pyruvate carboxylase and a-OADC indicate that these proteins are evolutionarily distinct from the acylCoA carboxylases. 89 Urea amidolyase is different from all other enzymes of this family and appears to be a recently evolved biotin-dependent enzyme present in only a subset of bacteria, algae, and fungi. 89,90 Structures of the carboxyltransferase domains of pyruvate carboxylase, a-OADC, 5sTC, and urea amidolyase have been reported, revealing that catalysis in this sub-group does not utilize an oxyanion hole to stabilize either biotin or the keto acid substrate.…”

“…89 Urea amidolyase is different from all other enzymes of this family and appears to be a recently evolved biotin-dependent enzyme present in only a subset of bacteria, algae, and fungi. 89,90 Structures of the carboxyltransferase domains of pyruvate carboxylase, a-OADC, 5sTC, and urea amidolyase have been reported, revealing that catalysis in this sub-group does not utilize an oxyanion hole to stabilize either biotin or the keto acid substrate. As such the exact mechanism by which the keto acid enolate is stabilized is unclear at the present time.…”

Pre-hybridisation: An efficient way of suppressing endogenous biotin-binding activity inherent to biotin–streptavidin detection system

“…Biotin is present in all eukaryotic cells where it acts as a cofactor for carboxylase enzymes such as acetyl-CoA carboxylase (220 kDa), pyruvate carboxylases (130 kDa), propionyl-CoA carboxylase (75 kDa) and 3-methyl crotonyl-CoA carboxylases (72 kDa) (Vaitaitis et al, 1999;Banks et al, 2003;Lombard and Moreira, 2011). Consequently, techniques based on biotin-avidin/streptavidin detection system suffer from a major drawback.…”