L-Homoserine
[CAS# 672-15-1]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Alpha--amino acid
• Name: L-Homoserine
• Synonyms: L-2-Amino-4-hydroxybutyric acid
• Molecular Formula: C₄H₉NO₃
• Molecular Weight: 119.12
• Protein Sequence: X
• CAS Registry Number: 672-15-1
• EC Number: 211-590-6
• SMILES: C(CO)[C@@H](C(=O)O)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 203 °C (Decomposes) (Expl.)
• Boiling point: 368.7±32.0 °C 760 mmHg (Calc.)^*
• Flash point: 176.8±25.1 °C (Calc.)^*
• Solubility: water: 1100 g/L (30 °C) (Expl.)
• Index of refraction: 1.511 (Calc.)^*
• Alpha: -8.5 ° (c=2, H2O 22 °C) (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2A	H319
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

L-Homoserine is a non-proteinogenic α-amino acid that serves as an important intermediate in the biosynthetic pathways of several essential amino acids, including threonine, methionine, and isoleucine. It is structurally similar to serine but contains an additional methylene group in its side chain, giving it the molecular formula C₄H₉NO₃. L-Homoserine is found naturally in microorganisms, plants, and some lower eukaryotes but is generally absent from animal proteins. In metabolic pathways such as the aspartate family amino acid pathway, L-homoserine is produced from aspartate via a sequence of enzymatic transformations involving aspartokinase and homoserine dehydrogenase.

The discovery of L-homoserine’s role in amino acid biosynthesis emerged from early 20th-century microbial nutrition studies. Researchers observed that certain bacteria and fungi required specific intermediates for growth in minimal media and identified L-homoserine as a critical precursor for threonine and methionine production. This discovery helped establish the metabolic links within the aspartate-derived amino acid family and clarified the role of feedback regulation in amino acid biosynthesis.

In nature, L-homoserine is synthesized from L-aspartate through phosphorylation to aspartyl phosphate, reduction to L-aspartate-4-semialdehyde, and subsequent NADPH-dependent reduction to L-homoserine. The molecule’s hydroxyl group allows further enzymatic modifications, such as phosphorylation to O-phospho-L-homoserine, a direct precursor for both threonine and methionine. These reactions occur in the cytosol of plants and microorganisms and are tightly regulated by feedback inhibition to balance amino acid supply.

Industrial applications of L-homoserine primarily involve its role as a fermentation product and chemical precursor. Microbial fermentation processes, using organisms such as *Corynebacterium glutamicum*, can be engineered to overproduce L-homoserine for subsequent conversion into other valuable amino acids. Its production is important in the synthesis of L-threonine and L-methionine for use in animal feed, food additives, and pharmaceutical intermediates. L-Homoserine can also serve as a starting material for synthetic routes to various bioactive compounds due to its functional groups, which facilitate further chemical transformations.

In biochemical research, L-homoserine is employed as a substrate in studies of amino acid biosynthesis enzymes, metabolic regulation, and stereospecific catalysis. Its availability in both natural and synthetic forms allows controlled experimental investigations of metabolic flux and enzyme specificity.

The stability of L-homoserine in aqueous solutions depends on pH and temperature, with the compound prone to slow degradation under strongly acidic or alkaline conditions. In commercial production, purification often involves crystallization or ion-exchange chromatography to achieve the high purity required for biochemical applications.

References

2005. Autoinduction in Erwinia amylovora: Evidence of an Acyl-Homoserine Lactone Signal in the Fire Blight Pathogen. Journal of Bacteriology, 187(9).
DOI: 10.1128/jb.187.9.3079-3087.2005
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1082833

1998. Cystathionine gamma-synthase from Arabidopsis thaliana: purification and biochemical characterization of the recombinant enzyme overexpressed in Escherichia coli. The Biochemical Journal, 331(Pt 2).
DOI: 10.1042/bj3310639
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219399

1971. The enzymic formation of O-acetylhomoserine in Bacillus subtilis and its regulation by methionine and S-adenosylmethionine. Biochemical and Biophysical Research Communications, 45(5).
DOI: 10.1016/0006-291x(71)90478-5
URL: https://pubmed.ncbi.nlm.nih.gov/5001847