title: Acetate kinase isozymes confer robustness in acetate metabolism.
abstract: Acetate kinase (ACK) (EC no: 2.7.2.1) interconverts acetyl-phosphate and acetate to either catabolize or synthesize acetyl-CoA dependent on the metabolic requirement. Among all ACK entries available in UniProt, we found that around 45% are multiple ACKs in some organisms including more than 300 species but surprisingly, little work has been done to clarify whether this has any significance. In an attempt to gain further insight we have studied the two ACKs (AckA1, AckA2) encoded by two neighboring genes conserved in Lactococcus lactis (L. lactis) by analyzing protein sequences, characterizing transcription structure, determining enzyme characteristics and effect on growth physiology. The results show that the two ACKs are most likely individually transcribed. AckA1 has a much higher turnover number and AckA2 has a much higher affinity for acetate in vitro. Consistently, growth experiments of mutant strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary physiological roles in L. lactis to maintain a robust acetate metabolism for fast growth at different extracellular acetate concentrations. The existence of ACK isozymes may reflect a common evolutionary strategy in bacteria in an environment with varying concentrations of acetate.
authors.affiliation: National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Siu Hung Joshua
authors.initials: SH
authors.lastname: Chan
authors.affiliation: National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Nørregaard
authors.affiliation: National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Solem
authors.affiliation: National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Peter Ruhdal
authors.initials: PR
authors.lastname: Jensen
mesh_terms: D000084:Acetate Kinase / Q000235:genetics / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism* / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000378:metabolism; D001483:Base Sequence; D017124:Conserved Sequence; D005798:Genes, Bacterial; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D013294:Lactococcus lactis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D008320:Maltose / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D019289:Pyruvic Acid / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013728:Terminator Regions, Genetic; D024363:Transcription Initiation Site
chemical_list: D000085:Acetates; D007527:Isoenzymes; D019344:Lactic Acid; D008320:Maltose; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D000084:Acetate Kinase