β-Ethynylserine
Chemical compound
From Wikipedia, the free encyclopedia
β-Ethynylserine (also known as beta-ethynylserine, 3-ethynylserine, or βES) is a non-proteinogenic amino acid containing a terminal alkyne group. It is produced by the bacteria Streptomyces cattleya. It functions as an antimetabolite of L-threonine and in the laboratory it is used as a bioorthogonal analog of threonine for metabolic labeling of proteins.
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| IUPAC name
(2S,3R)-2-Amino-3-hydroxypent-4-ynoic acid | |
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| Properties | |
| C5H7NO3 | |
| Molar mass | 129.115 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Occurrence
β-Ethynylserine was first isolated and reported in 1986 as a metabolite produced by the bacterium Streptomyces cattleya. It was identified as an antimetabolite of L-threonine.[1] The biosynthetic gene cluster responsible for its production in S. cattleya was identified and characterized in 2019.[2][3] In S. cattleya, β-ethynylserine is produced via a dedicated six-gene biosynthetic cluster (bes cluster). The pathway begins with L-lysine, which undergoes radical halogenation by BesD, a radical halogenase, followed by oxidative cleavage and transformations to yield L-propargylglycine. Two additional enzymes (BesA and BesE) then convert L-propargylglycine to β-ethynylserine through β-hydroxylation.[3][2] This pathway represents a novel mechanism for terminal alkyne formation in amino acids, distinct from fatty acid desaturation routes used for internal alkynes in other natural products.[3]
Structure and properties
β-Ethynylserine is structurally similar to L-threonine, but features a terminal ethynyl group (–C≡CH) instead of a methyl group at the β-carbon. Its molecular formula is C5H7NO3, with a molecular weight of 129.11 g/mol.[4] It exists as the L-isomer in biological contexts.
Biological activity
β-Ethynylserine acts as an antimetabolite of L-threonine, inhibiting the growth of certain bacterial strains.[1]
Uses
In 2023, β-ethynylserine was introduced as the key reagent in the THRONCAT (threonine-derived non-canonical amino acid tagging) method for metabolic labeling of proteins under standard cell culture conditions.[5] It is efficiently incorporated into nascent polypeptide chains in place of threonine during protein synthesis in eukaryotic cells. The terminal alkyne group enables subsequent bioorthogonal conjugation via copper-catalyzed azide-alkyne cycloaddition with fluorescent dyes, affinity tags, or other probes, allowing selective visualization, tracking, or enrichment of newly synthesized proteins.[5][6]