l -Homoserine
Names
IUPAC name
(S )-2-Amino-4-hydroxybutanoic acid
Identifiers
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
100.010.538
EC Number
UNII
InChI=1S/C4H9NO3/c5-3(1-2-6)4(7)8/h3,6H,1-2,5H2,(H,7,8)
Y Key: UKAUYVFTDYCKQA-UHFFFAOYSA-N
Y InChI=1/C4H9NO3/c5-3(1-2-6)4(7)8/h3,6H,1-2,5H2,(H,7,8)
Key: UKAUYVFTDYCKQA-UHFFFAOYAZ
Properties
C4 H9 NO3
Molar mass
119.12 g/mol
Melting point
203 °C (decomposes)
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2 CCH(NH2 )CH2 CH2 OH. L -Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additional -CH2 - unit into the backbone. Homoserine, or its lactone form, is the product of a cyanogen bromide cleavage of a peptide by degradation of methionine .
Homoserine is an intermediate in the biosynthesis of three essential amino acids : methionine , threonine (an isomer of homoserine), and isoleucine .[ 1] Its complete biosynthetic pathway includes glycolysis , the tricarboxylic acid (TCA) or citric acid cycle (Krebs cycle), and the aspartate metabolic pathway. It forms by two reductions of aspartic acid via the intermediacy of aspartate semialdehyde.[ 2] Specifically, the enzyme homoserine dehydrogenase , in association with NADPH , catalyzes a reversible reaction that interconverts L -aspartate-4-semialdehyde to L -homoserine. Then, two other enzymes, homoserine kinase and homoserine O-succinyltransferase use homoserine as a substrate and produce phosphohomoserine and O -succinyl homoserine respectively.[ 3]
Applications
Commercially, homoserine can serve as precursor to the synthesis of isobutanol and 1,4-butanediol .[ 4] Purified homoserine is used in enzyme structural studies.[ 5] Also, homoserine has played important roles in studies to elucidate peptide synthesis and synthesis of proteoglycan glycopeptides.[ 6] Bacterial cell lines can make copious amounts of this amino acid.[ 3] [ 4]
Biosynthesis
Homoserine is produced from aspartate via aspartate-4-semialdehyde, which is produced from β-phosphoaspartate. By the action of homoserine dehydrogenases , the semialdehyde is converted to homoserine.[ 7]
Biosynthesis pathway for homoserine.
L -Homoserine is substrate for homoserine kinase , yielding phosphohomoserine (homoserine-phosphate), which is converted to by threonine synthase to yield L -threonine.
Homoserine is converted to O -succinyl homoserine by homoserine O-succinyltransferase , a precursor to L -methionine.[ 8]
Homoserine allosterically inhibits aspartate kinase and glutamate dehydrogenase .[ 3] Glutamate dehydrogenase reversibly converts glutamate to α-ketoglutarate and α-ketoglutarate coverts to oxaloacetate through the citric cycle. Threonine acts as another allosteric inhibitor of aspartate kinase and homoserine dehydrogenase, but it is a competitive inhibitor of homoserine kinase.[ 8]
References
^ Tanaka M, Kishi T, Kinoshita S (September 1961). "Studies on the Synthesis of l -Amino Acids: Part III. A Synthesis of l -Homoserine from l -Aspartic Acid" . Agricultural and Biological Chemistry . 25 (9): 678–679. doi :10.1080/00021369.1961.10857862 . ISSN 0002-1369 .
^ Berg, J. M.; Stryer, L. et al. (2002), Biochemistry . W.H. Freeman. ISBN 0-7167-4684-0
^ a b c Liu P, Zhang B, Yao ZH, Liu ZQ, Zheng YG (October 2020). Zhou NY (ed.). "Multiplex Design of the Metabolic Network for Production of l-Homoserine in Escherichia coli" . Applied and Environmental Microbiology . 86 (20). Bibcode :2020ApEnM..86E1477L . doi :10.1128/AEM.01477-20 . PMC 7531971 . PMID 32801175 .
^ a b Huang JF, Zhang B, Shen ZY, Liu ZQ, Zheng YG (July 2018). "Metabolic engineering of E. coli for the production of O -succinyl-l-homoserine with high yield" . 3 Biotech . 8 (7): 310. doi :10.1007/s13205-018-1332-x . PMC 6037649 . PMID 30002999 .
^ Akai S, Ikushiro H, Sawai T, Yano T, Kamiya N, Miyahara I (February 2019). "The crystal structure of homoserine dehydrogenase complexed with l-homoserine and NADPH in a closed form". Journal of Biochemistry . 165 (2): 185–195. doi :10.1093/jb/mvy094 . PMID 30423116 .
^ Yang W, Ramadan S, Yang B, Yoshida K, Huang X (December 2016). "Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and a Sulfated Glycan Chain" . The Journal of Organic Chemistry . 81 (23): 12052–12059. doi :10.1021/acs.joc.6b02441 . PMC 5215661 . PMID 27809505 .
^ Viola, Ronald E. (2001). "The Central Enzymes of the Aspartate Family of Amino Acid Biosynthesis". Accounts of Chemical Research . 34 (5): 339–349. doi :10.1021/ar000057q . PMID 11352712 .
^ a b Petit C, Kim Y, Lee SK, Brown J, Larsen E, Ronning DR, et al. (January 2018). "Reduction of Feedback Inhibition in Homoserine Kinase (ThrB) of Corynebacterium glutamicum Enhances l-Threonine Biosynthesis" . ACS Omega . 3 (1): 1178–1186. doi :10.1021/acsomega.7b01597 . PMC 6045374 . PMID 30023797 .