The preparation of PQQ disodium salt involves many steps such as raw material selection, reaction optimization, purification and separation, salinization and so on. According to different sources, it can be divided into chemical synthesis and microbial fermentation.
PQQ Chemical Synthesis Method
Fundamental principle
The chemical synthesis method uses chemical reagents as raw materials to synthesize PQQ through multi-step reaction by artificially designing the synthesis path. Finally, the PQQ disodium salt was prepared by neutralization reaction.
Process flow
Selection of raw materials: simple small molecular compounds (such as quinones and pyrroles) are used as starting materials.
Key reaction: the core structure of pyrroloquinoline quinone is generated by ammoniation of quinones.
Salinization treatment: the synthesized PQQ reacts with sodium hydroxide or sodium carbonate to prepare disodium salt form.
Purification and separation: crystallization, centrifugation or column chromatography are used to improve the purity of the product.
Advantages and disadvantages
Advantages: The chemical synthesis process is mature, the raw materials are easily available, and large-scale production can be realized.
Disadvantages: chemical synthesis needs more organic solvents, and the process may produce toxic by-products, which is not friendly to the environment. In addition, there are many steps and the yield is low.
Application status
Due to the high cost and great pressure of environmental protection, chemical synthesis method is more used for the preparation of PQQ disodium salt in laboratory scale or under specific conditions. Its industrial application is less.
PQQ Microbial Fermentation Method
Fundamental principle
Microbial fermentation method uses the natural PQQ in the metabolites of some bacteria (such as Methylobacter or Pseudomonas), and transforms it into available PQQ disodium salt by optimizing fermentation conditions and extraction process.
Process flow
Screening of strains: Select strains that can efficiently synthesize PQQ. Commonly used strains include Methylobacterium extorquens and Pseudomonas putida.
Fermentation culture: liquid fermentation is used to culture the bacteria under the conditions of specific carbon source, nitrogen source and trace elements, so that they secrete PQQ into the fermentation broth.
Extraction and separation: the bacteria were removed by centrifugation, and PQQ in the fermentation broth was extracted by adsorption resin or solvent.
Salinization treatment: the purified PQQ is neutralized with sodium salt to obtain PQQ disodium salt.
Drying and crystallization: freeze-drying or spray-drying the purified PQQ disodium salt solution to prepare powder.
Key technology
Fermentation process optimization: including adjusting the composition of culture medium, pH value and dissolved oxygen water equality, and improving PQQ yield.
Improvement of purification technology: Improve product purity through advanced separation technology (such as membrane separation, ultrafiltration or high performance liquid chromatography).
Genetic engineering transformation: the strain was improved by gene editing technology to enhance the activity of key enzymes in PQQ synthesis pathway.
Advantages and disadvantages
Advantages: The fermentation method is more environment-friendly, low in energy consumption, suitable for large-scale production and high in product purity.
Disadvantages: the fermentation period is long, which is easily affected by the strain state and environmental conditions, and there is some instability.
Application status
Microbial fermentation is currently the mainstream method for industrial production of PQQ disodium salt. Its stability and expansibility make it occupy an important position in market promotion.
At present, the extraction and production of PQQ disodium salt mainly depend on chemical synthesis and microbial fermentation. These two methods have their own advantages in yield, cost and environmental friendliness.