The industrial production process of L-valine

I. Mainstream Processes for Industrial Production

1. Microbial Fermentation (Core Process)

Strain Breeding: Improving strains such as Corynebacterium glutamicum and E. coli through genetic engineering or mutagenesis to enhance L-valine synthesis capacity (e.g., knocking out competitive pathway genes and strengthening precursor metabolic flux).

Fermentation Medium Optimization: Using glucose, corn steep liquor, ammonium sulfate, etc., as carbon and nitrogen sources, adding inorganic salts (such as dipotassium hydrogen phosphate) and growth factors (biotin, thiamine), controlling pH at 6.5-7.2 and temperature at 30-35°C. Fed-batch fermentation is adopted (supplementing glucose to maintain carbon source concentration), with a fermentation cycle of 48-72 hours and a yield of 80-100 g/L.

Separation and Purification:

The fermentation broth is centrifuged or filtered through a plate-and-frame filter to remove bacteria, and the supernatant is adsorbed by cation exchange resin (such as 732 resin), then eluted with ammonia water to obtain a crude product solution.

The crude product is decolorized with activated carbon, purified by ultrafiltration, concentrated by evaporation, cooled and crystallized (controlling the temperature at 20-30°C), and the L-valine crystals are obtained by centrifugal separation. Finally, the finished product is obtained by airflow drying (temperature 80-100°C) with a purity of ≥99%.

2. Enzymatic Conversion (Auxiliary Process)

Using α-ketoisovalerate as a substrate, the amination reaction is catalyzed by transaminase (such as transaminase from Bacillus subtilis), with pyridoxal phosphate (PLP) as a coenzyme. The reaction system needs to maintain ammonium ion concentration (such as ammonium sulfate), pH 7.0-8.0, temperature 35-40°C, with a conversion rate of over 90%. The product is purified by membrane separation and crystallization.

3. Chemical Synthesis (Less Applied)

Using isobutyraldehyde as the starting material, it is synthesized through steps such as cyanoalcoholation, ammonolysis, and hydrolysis. Highly toxic reagents (such as hydrocyanic acid) are required. The steps are tedious, the optical purity of the product is low (DL-valine needs to be resolved), the cost is high, and the environmental pressure is great. It is only used in special scenarios.

II. Key Links in Cost Control

1. Raw Material Cost Optimization

Carbon Source Substitution: Replacing glucose with starch hydrolysate (corn starch) or using industrial waste (such as molasses, lignocellulose hydrolysate) reduces costs by 10%-15%, but the ability of strains to utilize complex carbon sources needs to be optimized.

Nitrogen Source Recovery: Ammonia nitrogen in the fermentation waste liquid is recovered by ion exchange resin and used to prepare new media, increasing nitrogen source utilization by 20%.

2. Improvement of Fermentation Efficiency

Intelligent Process Control: By online monitoring of dissolved oxygen (DO), pH, and substrate concentration, real-time adjustment of stirring speed, air volume, and feeding rate reduces substrate waste and increases yield by 5%-8%.

High-Density Fermentation: Using fed-batch culture technology to maintain the cell concentration at 50-80 g/L (dry weight), extending the product synthesis period and increasing the unit volume yield by 30%.

3. Improvement of Separation and Purification Processes

Resin Regeneration Optimization: Cation exchange resin uses staged elution (low-concentration ammonia water → high-concentration ammonia water) to reduce the amount of eluent, extend the resin life to more than 500 times, and reduce costs by 15%.

Crystallization Process Optimization: Using an ethanol-water mixed solvent instead of a pure water solution for crystallization reduces the solubility difference, increases the crystallization yield from 75% to 85%, and shortens the crystallization time.

4. Energy and Environmental Protection Cost Control

Steam Heat Recovery: The waste heat generated in the drying process is used to preheat the fermentation medium, reducing energy consumption by 10%-15%.

Integrated Wastewater Treatment: Fermentation waste liquid is reused after anaerobic digestion (biogas production) and aerobic treatment, reducing water treatment costs. At the same time, biogas can replace part of the coal, reducing comprehensive costs by 8%-10%.

III. Industry Cost Comparison and Bottlenecks

Cost Composition

Raw materials (carbon and nitrogen sources): about 40%-50%

Energy (steam, electricity): 20%-25%

Equipment depreciation and labor: 15%-20%

Environmental protection treatment: 5%-10%

Scale Effect

The unit cost of a production line with an annual output of more than 10,000 tons is 20%-30% lower than that of a thousand-ton level due to stronger equipment allocation and raw material procurement bargaining power.

Technical Bottlenecks

High-concentration substrate inhibition (bacterial growth is inhibited when glucose > 50 g/L)

Product loss in the separation and purification process (about 5%-8%)

These remain key challenges for cost optimization, which need to be overcome through strain modification (such as enhancing sugar tolerance genes) and new separation technologies (such as membrane distillation).

Through full-process optimization and digital management, the current production cost of L-valine for mainstream enterprises can be controlled at 20-25 yuan/kg. With the progress of synthetic biology technologies (such as the construction of de novo synthesis pathways), the cost is expected to further decrease by 10%-15% in the future.