Abstract
Threonine aldolases (TAs) catalyze the interconversion of threonine and glycine plus acetaldehyde in a pyridoxal phosphate-dependent manner. This class of enzymes complements the primary glycine biosynthetic pathway catalyzed by serine hydroxymethyltransferase (SHMT), and was shown to be necessary for yeast glycine auxotrophy. Because the reverse reaction of TA involves carbon–carbon bond formation, resulting in a β-hydroxyl-α-amino acid with two adjacent chiral centers, TAs are of high interests in synthetic chemistry and bioengineering studies. Here, we report systematic phylogenetic analysis of TAs. Our results demonstrated that l-TAs and d-TAs that are specific for l- and d-threonine, respectively, are two phylogenetically unique families, and both enzymes are different from their closely related enzymes SHMTs and bacterial alanine racemases (ARs). Interestingly, l-TAs can be further grouped into two evolutionarily distinct families, which share low sequence similarity with each other but likely possess the same structural fold, suggesting a convergent evolution of these enzymes. The first l-TA family contains enzymes of both prokaryotic and eukaryotic origins, and is related to fungal ARs, whereas the second contains only prokaryotic l-TAs. Furthermore, we show that horizontal gene transfer may occur frequently during the evolution of both l-TA families. Our results indicate the complex, dynamic, and convergent evolution process of TAs and suggest an updated classification scheme for l-TAs.
This is a preview of subscription content, log in via an institution to check access.
References
Anisimova M, Gascuel O (2006) Approximate likelihood-ratio test for branches: a fast, accurate, and powerful alternative. Syst Biol 55:539
Atkinson HJ, Morris JH, Ferrin TE, Babbitt PC (2009) Using sequence similarity networks for visualization of relationships across diverse protein superfamilies. PLoS ONE 4:e4345
Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I, Creech M, Gross B, Hanspers K, Isserlin R, Kelley R, Killcoyne S, Lotia S, Maere S, Morris J, Ono K, Pavlovic V, Pico AR, Vailaya A, Wang PL, Adler A, Conklin BR, Hood L, Kuiper M, Sander C, Schmulevich I, Schwikowski B, Warner GJ, Ideker T, Bader GD (2007) Integration of biological networks and gene expression data using cytoscape. Nat Protoc 2:2366
Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D’Aguanno S, Bossa F (2001) l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase—a subgroup of strictly related enzymes specialized for different functions. Eur J Biochem 268:6508
di Salvo ML, Remesh SG, Vivoli M, Ghatge MS, Paiardini A, D’Aguanno S, Safo MK, Contestabile R (2014) On the catalytic mechanism and stereospecificity of Escherichia coli l-threonine aldolase. FEBS J 281:129
Duckers N, Baer K, Simon S, Groger H, Hummel W (2010) Threonine aldolases-screening, properties and applications in the synthesis of non-proteinogenic beta-hydroxy-alpha-amino acids. Appl Microbiol Biotechnol 88:409
Edgar AJ (2005) Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene. BMC Genom 6:32
Eliot AC, Kirsch JF (2004) Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu Rev Biochem 73:383
Fesko K, Reisinger C, Steinreiber J, Weber H, Schurmann M, Griengl H (2008) Four types of threonine aldolases: similarities and differences in kinetics/thermodynamics. J Mol Catal B-Enzym 52–3:19
Franz SE, Stewart JD (2014) Threonine aldolases. Adv Appl Microbiol 88:57
Gish W, States DJ (1993) Identification of protein coding regions by database similarity search. Nat Genet 3:266
Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696
Hayashi H (1995) Pyridoxal enzymes: mechanistic diversity and uniformity. J Biochem 118:463
Jander G, Norris SR, Joshi V, Fraga M, Rugg A, Yu S, Li L, Last RL (2004) Application of a high-throughput HPLC-MS/MS assay to arabidopsis mutant screening; evidence that threonine aldolase plays a role in seed nutritional quality. Plant J 39:465
Kataoka M, Ikemi M, Morikawa T, Miyoshi T, Nishi K, Wada M, Yamada H, Shimizu S (1997a) Isolation and characterization of d-threonine aldolase, a pyridoxal-5′-phosphate-dependent enzyme from Arthrobacter sp. DK-38. Eur J Biochem 248:385
Kataoka M, Wada M, Nishi K, Yamada H, Shimizu S (1997b) Purification and characterization of L-allo-threonine aldolase from aeromonas jandaei DK-39. FEMS Microbiol Lett 151:245
Kielkopf CL, Burley SK (2002) X-ray structures of threonine aldolase complexes: structural basis of substrate recognition. Biochemistry 41:11711
Liu JQ, Dairi T, Kataoka M, Shimizu S, Yamada H (1997a) L-allo-threonine aldolase from Aeromonas jandaei DK-39: gene cloning, nucleotide sequencing, and identification of the pyridoxal 5′-phosphate-binding lysine residue by site-directed mutagenesis. J Bacteriol 179:3555
Liu JQ, Nagata S, Dairi T, Misono H, Shimizu S, Yamada H (1997b) The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific l-threonine aldolase that catalyzes cleavage of L-allo-threonine and l-threonine to glycine–expression of the gene in Escherichia coli and purification and characterization of the enzyme. Eur J Biochem 245:289
Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (1998a) Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity l-threonine aldolase from Escherichia coli. Eur J Biochem 255:220
Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (1998b) A novel metal-activated pyridoxal enzyme with a unique primary structure, low specificity d-threonine aldolase from Arthrobacter sp. Strain DK-38. Molecular cloning and cofactor characterization. J Biol Chem 273:16678
Liu JQ, Ito S, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (1998c) Gene cloning, nucleotide sequencing, and purification and characterization of the low-specificity l-threonine aldolase from Pseudomonas sp. strain NCIMB 10558. Appl Environ Microbiol 64:549
Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (2000a) Diversity of microbial threonine aldolases and their application. J Mol Catal B-Enzym 10:107
Liu JQ, Odani M, Yasuoka T, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (2000b) Gene cloning and overproduction of low-specificity d-threonine aldolase from Alcaligenes xylosoxidans and its application for production of a key intermediate for parkinsonism drug. Appl Microbiol Biotechnol 54:44
Lukk T, Sakai A, Kalyanaraman C, Brown SD, Imker HJ, Song L, Fedorov AA, Fedorov EV, Toro R, Hillerich B, Seidel R, Patskovsky Y, Vetting MW, Nair SK, Babbitt PC, Almo SC, Gerlt JA, Jacobson MP (2012) Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily. Proc Natl Acad Sci 109:4122
Mau B, Newton MA, Larget B (1999) Bayesian phylogenetic inference via Markov chain Monte Carlo methods. Biometrics 55:1
McNeil JB, McIntosh EM, Taylor BV, Zhang FR, Tang S, Bognar AL (1994) Cloning and molecular characterization of three genes, including two genes encoding serine hydroxymethyltransferases, whose inactivation is required to render yeast auxotrophic for glycine. J Biol Chem 269:9155
Paiardini A, Contestabile R, D’Aguanno S, Pascarella S, Bossa F (2003) Threonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes. Biochim Biophys Acta 1647:214
Pruitt KD, Tatusova T, Maglott DR (2007) NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 35:D61
Qin HM, Imai FL, Miyakawa T, Kataoka M, Kitamura N, Urano N, Mori K, Kawabata H, Okai M, Ohtsuka J, Hou F, Nagata K, Shimizu S, Tanokura M (2014) L-allo-threonine aldolase with an H128Y/S292R mutation from Aeromonas jandaei DK-39 reveals the structural basis of changes in substrate stereoselectivity. Acta Crystallogr D Biol Crystallogr 70:1695
Ronquist F, Teslenko M, van der Mark P, Ayres DL, Darling A, Hohna S, Larget B, Liu L, Suchard MA, Huelsenbeck JP (2012) MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst Biol 61:539
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731
Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876
Whelan S, Goldman N (2001) A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol 18:691
Zhao S, Sakai A, Zhang X, Vetting MW, Kumar R, Hillerich B, San Francisco B, Solbiati J, Steves A, Brown S, Akiva E, Barber A, Seidel RD, Babbitt PC, Almo SC, Gerlt JA, Jacobson MP (2014) Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks. Elife 3:e03275
Acknowledgments
This work was supported in part by grants from National Natural Science Foundation (2011DFA32520 to M.Z.), from State Key Laboratory of Bioorganic Chemistry (SKLBNPC13425 to W.D.), and from Fudan University (IDH1615002 to Q.Z). Q.Z would also like to thank the support of the Thousand Talents Program.
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Liu, G., Zhang, M., Chen, X. et al. Evolution of Threonine Aldolases, a Diverse Family Involved in the Second Pathway of Glycine Biosynthesis. J Mol Evol 80, 102–107 (2015). https://doi.org/10.1007/s00239-015-9667-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-015-9667-y