Valienone (BioDeep_00000011831)

描述信息

A member of the class of cyclohexenones that is cyclohex-2-en-1-one substituted by hydroxy groups at positions 4, 5 and 6, and by a hydroxymethyl group at position 3 (the 4R,5S,6R-diastereomer).

Valienone is a member of the class of cyclohexenones that is cyclohex-2-en-1-one substituted by hydroxy groups at positions 4, 5 and 6, and by a hydroxymethyl group at position 3 (the 4R,5S,6R-diastereomer). It has a role as a bacterial xenobiotic metabolite. It is a member of cyclohexenones, an enone and a tetrol. It is functionally related to a valiolone.

Valienone is a biologically significant compound with the following key biological functions:

### 1. **Biosynthetic Precursor in Drug Synthesis**
Valienone serves as a **critical intermediate** in the biosynthesis of β-valienamine and valienamine. These derivatives are potent **β-glycosidase inhibitors**, which are essential for:
• **Treating lysosomal storage diseases**: β-valienamine derivatives (e.g., N-octyl-β-valienamine) specifically target β-glycosidase dysfunction, a hallmark of lysosomal storage disorders.
• **Diabetes management**: Valienamine is the active component of acarbose, a drug used to control blood glucose levels by inhibiting carbohydrate-digesting enzymes.

### 2. **Enzymatic Substrate in Stereoselective Reactions**
Valienone is a substrate for **aminotransferases** (e.g., BtrR from *Bacillus circulans*), which catalyze its conversion to β-valienamine with high stereoselectivity. This reaction involves:
• **Pyridoxal phosphate (PLP)-dependent transamination**: Ensures optical purity of the product (enantiomeric excess value).
• **Regulation of enzyme stability and activity**: Molecular dynamics simulations show that β-valienamine enhances the stability of BtrR and optimizes its catalytic tunnel for efficient product release.

### 3. **Role in Microbial Metabolism**
Valienone is naturally produced by microbial strains (e.g., *Streptomyces* spp.) as part of the **biosynthetic pathway for aminoglycoside antibiotics** like validamycin A. Its microbial production avoids the challenges of chemical synthesis, such as poor stereospecificity and complex reaction steps.

### 4. **Structural Basis for Drug Design**
The **hexacyclic polyol-ketone structure** of valienone provides a scaffold for developing:
• **Chiral therapeutics**: Its four stereocenters enable precise interactions with biological targets.
• **Enzyme inhibitors**: Modifications to its core structure enhance binding to glycosidases or other enzymes involved in metabolic diseases.

### References
: Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Molecular Dynamics (PMC, 2025)
: Efficient Synthesis of Valienamine via Directed Evolution of Aminotransferases (*ACS Catal.*, 2022)

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