Isochorismic acid
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Product Description
Isochorismic acid, also known as isochorismate, is a pivotal dibasic organic acid (C₁₀H₁₀O₆; 226.184 g/mol) that occupies a strategic branch-point in the shikimate pathway of bacteria and plants. This combination of low dielectric character, thermal stability, and facile polymerization makes the molecule a valued building block for advanced photoresists and high-performance low-k resins in micro- and opto-electronic applications.
Other Information
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Biological Redundancy: Arabidopsis thaliana and some other plants have two functional ICS genes (AtICS1 and AtICS2) with very similar enzymatic properties but different expression patterns. This gene duplication may provide an evolutionary advantage, such as functional redundancy for essential pathways (e.g., phylloquinone synthesis) or specialized roles (e.g., AtICS2 being constitutively expressed in vasculature for basal defense).
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Monofunctional Enzyme: Plant and many bacterial ICS enzymes are monofunctional, meaning they only convert chorismate to isochorismate. They lack isochorismate pyruvate lyase (IPL) activity, which is required to directly produce salicylate. Therefore, a separate IPL enzyme (which remains unidentified in plants) or an alternative route (like the PBS3 pathway) is necessary to complete SA biosynthesis.
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Evolutionary Note: The existence of monofunctional ICS enzymes in plants, as opposed to bifunctional SAS (Salicylate Synthase) enzymes found in some bacteria, may be an evolutionary adaptation to prevent the uncontrolled drainage of the chorismate pool, which is also needed for synthesizing essential amino acids and other metabolites.
Synthesis and Production
Isochorismic acid is primarily produced through enzymatic biosynthesis within living organisms as part of the shikimate pathway. Its synthesis is tightly regulated and compartmentalized.
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Biosynthetic Precursor: It is synthesized directly from chorismic acid.
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Key Enzyme: The conversion is catalyzed by the enzyme Isochorismate Synthase (ICS) (EC 5.4.4.2, also known as chorismate hydroxymutase).
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Reaction Characteristics:
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The reaction is reversible and operates near equilibrium (K_eq ≈ 0.89), slightly favoring chorismate.
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It is absolutely Mg²⁺-dependent, with a K_m for Mg²⁺ in the micromolar range (e.g., 0.193 mM for AtICS1, 0.55-0.94 mM for Arabidopsis ICS enzymes).
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Cellular Location:
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In plants like Arabidopsis thaliana, this synthesis occurs in the plastid (chloroplast) stroma. The ICS enzymes contain a chloroplast transit peptide for import.
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In bacteria, it also occurs in the cytoplasm.
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Heterologous Production: For research, recombinant ICS enzymes (e.g., from Arabidopsis AtICS1 and AtICS2) can be expressed in E. coli and purified to produce isochorismate from chorismate in vitro. Successful expression sometimes requires specific conditions, such as the addition of ethanol to the culture medium to aid protein folding.
Uses and Applications
Isochorismic acid itself is not a final product but a critical biochemical intermediate. Its primary "application" is in nature, where it serves as a branch-point precursor for the biosynthesis of several important compounds.
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Salicylic Acid (SA) Biosynthesis: This is a major application in plants.
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SA is a crucial plant hormone that regulates defense responses against pathogens (Systemic Acquired Resistance) and abiotic stress.
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The pathway involves ICS converting chorismate to isochorismate in the plastid. Isochorismate is then exported to the cytosol and converted to SA via enzymes like PBS3, which produces an unstable intermediate (isochorismate-9-glutamate) that decomposes to SA.
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Siderophore Production: In bacteria (e.g., Pseudomonas aeruginosa, E. coli), isochorismate is a key intermediate in the biosynthesis of iron-chelating siderophores, such as enterobactin and pyochelin, which are essential for scavenging iron.
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Vitamin Biosynthesis: It is a precursor for:
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Menaquinones (Vitamin K₂) in bacteria.
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Phylloquinone (Vitamin K₁) in plants, where it acts as an electron acceptor in Photosystem I.
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Other Specialized Metabolites: It serves as a building block for various alkaloids, phenazines, and anthraquinones in different organisms.
Chemical and Physical Properties
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Molecular Formula: C₁₀H₁₀O₆
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Molar Mass: 226.18 g/mol
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IUPAC Name: (5S,6S)-5-((1-Carboxyethenyl)oxy)-6-hydroxy-1,3-cyclohexadiene-1-carboxylic acid
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CAS Number: 22642-82-6
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Solubility: Highly soluble in water due to multiple polar functional groups (carboxylic acids, hydroxyl group).
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Chemical Instability: It is unstable in neutral aqueous solution at room temperature, spontaneously rearranging via a [3,3]-sigmatropic shift to form other products, including salicylate derivatives.
Structural Characteristics
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Core Structure: A cyclohexa-1,3-diene ring.
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Functional Groups:
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Two carboxylic acid groups (-COOH).
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One hydroxyl group (-OH) at the 6-position.
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An enol ether side chain at the 5-position, featuring a vinyl group connected to another carboxylic acid.
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Stereochemistry: It has two chiral centers (carbons 5 and 6), both in the (S) configuration, which is essential for its biological activity and enzyme recognition.
Biochemical and Kinetic Properties (from Enzyme Studies)
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ICS Enzyme Kinetics (from Arabidopsis):
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K_m for Chorismate: Similar for both ICS1 (34.3 µM) and ICS2 (28.8 µM).
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Catalytic Efficiency: ICS1 (k_cat/K_m = 1.11 µM⁻¹ min⁻¹) is roughly twice as efficient as ICS2 (0.59 µM⁻¹ min⁻¹), primarily due to a higher turnover rate (k_cat).
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Temperature Optimum: ~33°C, with significant activity across a broad range (from 4°C to 44°C).
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pH Optimum: Slightly basic, around pH 7.5-8.0.
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Safety and Handling
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General Precautions: Assume it should be handled with care. Use personal protective equipment (PPE) including gloves and safety glasses.
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Storage: Based on its instability, it should be stored at low temperatures (e.g., -80°C) and potentially at controlled pH to prevent decomposition.