:Homoserine
{{chembox
| Verifiedimages = changed
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 461770636
| Name = {{sm|l}}-Homoserine
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageFile = L-Homoserin.svg
| ImageSize = 180px
| ImageName = Skeletal formula
| ImageFile1 = L-Homoserine-zwitterion-3D-balls.png
| ImageSize1 = 120px
| ImageName1 = Ball-and-stick model of the zwitterion
| IUPACName = (S)-2-Amino-4-hydroxybutanoic acid
|Section1={{Chembox Identifiers
| InChI = 1/C4H9NO3/c5-3(1-2-6)4(7)8/h3,6H,1-2,5H2,(H,7,8)
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 30653
| SMILES = O=C(O)C(N)CCO
| InChIKey = UKAUYVFTDYCKQA-UHFFFAOYAZ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H9NO3/c5-3(1-2-6)4(7)8/h3,6H,1-2,5H2,(H,7,8)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UKAUYVFTDYCKQA-UHFFFAOYSA-N
| CASNo = 672-15-1
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6KA95X0IVO
| EC_number = 211-590-6
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 758
| PubChem = 779
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 11722
}}
|Section2={{Chembox Properties
| Formula = C4H9NO3
| MolarMass = 119.12 g/mol
| MeltingPt = 203 °C (decomposes)
}}
}}
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. 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 methylene bridge into the sidechain. Homoserine, or its lactone, 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.{{Cite journal| vauthors = Tanaka M, Kishi T, Kinoshita S |date=September 1961|title=Studies on the Synthesis of l -Amino Acids: Part III. A Synthesis of l -Homoserine from l -Aspartic Acid|url=https://academic.oup.com/bbb/article/25/9/678-679/5976039|journal=Agricultural and Biological Chemistry|language=en|volume=25|issue=9|pages=678–679|doi=10.1080/00021369.1961.10857862|issn=0002-1369|url-access=subscription}}
Applications
Commercially, homoserine can serve as precursor to the synthesis of isobutanol and 1,4-butanediol.{{cite journal | vauthors = Huang JF, Zhang B, Shen ZY, Liu ZQ, Zheng YG | title = Metabolic engineering of E. coli for the production of O-succinyl-l-homoserine with high yield | journal = 3 Biotech | volume = 8 | issue = 7 | pages = 310 | date = July 2018 | pmid = 30002999 | pmc = 6037649 | doi = 10.1007/s13205-018-1332-x }} Purified homoserine is used in enzyme structural studies.{{cite journal | vauthors = Akai S, Ikushiro H, Sawai T, Yano T, Kamiya N, Miyahara I | title = The crystal structure of homoserine dehydrogenase complexed with l-homoserine and NADPH in a closed form | journal = Journal of Biochemistry | volume = 165 | issue = 2 | pages = 185–195 | date = February 2019 | pmid = 30423116 | doi = 10.1093/jb/mvy094 }} Also, homoserine has played important roles in studies to elucidate peptide synthesis and synthesis of proteoglycan glycopeptides.{{cite journal | vauthors = Yang W, Ramadan S, Yang B, Yoshida K, Huang X | title = Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and a Sulfated Glycan Chain | journal = The Journal of Organic Chemistry | volume = 81 | issue = 23 | pages = 12052–12059 | date = December 2016 | pmid = 27809505 | doi = 10.1021/acs.joc.6b02441 | pmc = 5215661 }} Bacterial cell lines can make copious amounts of this amino acid.
Biosynthesis
Its complete biosynthetic pathway includes glycolysis, the tricarboxylic acid (TCA) or citric acid cycle (Krebs cycle), and the aspartate metabolic pathway.{{huh?|date=May 2025}} It forms by two reductions of aspartic acid via the intermediacy of aspartate semialdehyde.Berg, J. M.; Stryer, L. et al. (2002), Biochemistry. W.H. Freeman. {{ISBN|0-7167-4684-0}} Specifically, the enzyme homoserine dehydrogenase, in association with NADPH, catalyzes a reversible reaction that interconverts L-aspartate-4-semialdehyde to L-homoserine.
Homoserine kinase and homoserine O-succinyltransferase convert homoserine to phosphohomoserine and O-succinyl homoserine, respectively.{{cite journal | vauthors = Liu P, Zhang B, Yao ZH, Liu ZQ, Zheng YG | title = Multiplex Design of the Metabolic Network for Production of l-Homoserine in Escherichia coli | journal = Applied and Environmental Microbiology | volume = 86 | issue = 20 | date = October 2020 | pmid = 32801175 | doi = 10.1128/AEM.01477-20 | pmc = 7531971 | bibcode = 2020ApEnM..86E1477L | veditors = Zhou NY }}
Homoserine is produced from aspartate via the intermediate aspartate-4-semialdehyde, which is produced from β-phosphoaspartate. By the action of homoserine dehydrogenases, the semialdehyde is converted to homoserine.{{cite journal |doi=10.1021/ar000057q|title=The Central Enzymes of the Aspartate Family of Amino Acid Biosynthesis |year=2001 |last1=Viola |first1=Ronald E. |journal=Accounts of Chemical Research |volume=34 |issue=5 |pages=339–349 |pmid=11352712 }}
Other biochemical roles
L-Homoserine is substrate for homoserine kinase, yielding phosphohomoserine (homoserine-phosphate), which is converted by threonine synthase to L-threonine.
Homoserine is converted to O-succinyl homoserine by homoserine O-succinyltransferase. O-succinyl homoserine is a precursor to L-methionine.{{cite journal | vauthors = Petit C, Kim Y, Lee SK, Brown J, Larsen E, Ronning DR, Suh JW, Kang CM | display-authors = 6 | title = Reduction of Feedback Inhibition in Homoserine Kinase (ThrB) of Corynebacterium glutamicum Enhances l-Threonine Biosynthesis | journal = ACS Omega | volume = 3 | issue = 1 | pages = 1178–1186 | date = January 2018 | pmid = 30023797 | doi = 10.1021/acsomega.7b01597 | pmc = 6045374 }}
Homoserine inhibits aspartate kinase and glutamate dehydrogenase. 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.