PQQ (Methoxatin disodium Salt) was originally found in nature as a coenzyme for enzymes with a small number of bacteria, including methylotrophic bacteria. Hence it is due to, on the first hand, that it is found in some natural products (such as fermented soy products, natto is one of them, green tea, kiwifruit but also in human milk, though in tiny amounts in food roughly corresponding to in the diet hangs breitennterans nanograms) and on the other it hand because of efficiency. Secondly, in response to the need for nutrition supplementation, it can be manufactured by chemical synthesis or modern industrial biosynthesis, for example, via certain genetically engineered bacteria (e.g., Methylobacterium). The second method is simple and sustainable, and it is the main source of commercial PQQ nowadays.

Nature Foods

Pyrroloquinoline quinone is widely distributed in nature, being present in prokaryotes as well as plants and animals. Prokaryotic Sources: PQQ is a redox cofactor in a vast number of bacterial enzymes,These soil bacteria are the major natural producers of PQQ, infiltrate the food chain. Eukaryotic Sources Few foods contain PQQ in trace amounts (ng – μg/g). Its detection in plants and animals is attributed to microbial synthesis and dietary accumulatio.

The following table presents the content of PQQ in some common sources of diet:

Industrial Production

Commercial scale production methods have been established in two main areas, biotechnology on the rise.

Chemical Synthesis:

PQQ disodium Salt is synthesized from the 6-amino-5-methoxy-1H-indole-2-carboxylic acid ethyl ester and dimethyl 2-oxopentenedioate as the raw material. In the process through a number of important steps, including coupling and cyclization of the primary cycle, then the quinoline ring system is constructed. Following steps are oxidation to introduce quinone moiety and ester hydrolysis to transform ester groups to carboxylic acids. Finally, the product is purified. Hazardous chemical solvent, DCM, is used throughout SOP and the complicated reaction routine certainly bring about various unknown impurites.These chemically derived impurities are not exist in nature in human body and there is a potential risk of them accumulating in human body which may lead to unidentified diseases in future.They are involved in complex reactions that produce a variety of unknown byproducts, chemical or otherwise,Hmm. In addition, the chemical synthesis of PQQ disodium salt powder is associated with some environmental pollution. The chemical synthesis of PQQ supplement, therefore, is not without (great) difficulties. 

Microbial Fermentation:

In Nature, pqq vitamin is only produced by a few bacteria, most of those are Gram-negative. Most bacteria have this essential substance in their cell membrane, but they cannot make it themselves; Similarly Higher Plants and Animals must obtain it from external supply. That is why towards the natural world, PQQ ingredient is “deficient”, yet vitally necessary.

Screen for natural strains of bacteria that are safe and stable to produce PQQ powder in industrial quantities. Several rigorous requirements must be met for a perfect strain: it is safe to consume, no toxic or harmful secondary metabolites are produced, it can express a significant amount of pqq supplement, and extracellular PQQ with a light fermentation supernant)

With these stringent requirements, methylotrophic bacteria were pinpointed as applicants, represented by Hyphomicrobium denitrificans and Methylobacterium extorquens. Among these the most common application is for Hyphomicrobium denitrificans.

Firstly, these strains proved to be biologically safe. Secondly, methylotrophic bacteria have no glycolytic pathway, and use one-carbon compounds, e.g. methanol and methylamine, directly oxidized and assimilated. PQQ is an important coenzyme in these metabolic processes. Thus, pqq supplement is directly integrated, and essential, in their core metabolic process. In addition, PQQ is loosely attached to the center of the enzyme by calcium and magnesium ions, and can be easily detached. This novel mechanism is responsible for the extraordinarily high levels of PQQ expression in these strains. 

In the end, a continuous synthesis is still needed, since intracellular PQQ in these bacteria is insufficient because of active secretion, requiring constant production to make up for loss. That steady output is exactly what scientists want to get. Plus, since no organic nitrogen source or sugars need to be added for fermentation, they are not mixed with the impurities and amino acids. This not only reduces the extracellular degradation of PQQ but also greatly makes easier the downstream purification.

When it comes to production, it is the extraction and purification process that proves to be the challenge, whether PQQ Powder is synthesized chemically or fermented through microbes. Curiously, in this respect, downstream purification is essentially the same, and ends in convergence these two routes of production. Generally, the following core procedures are involved, isolating the desired PQQ from the reactant mixture or fermentation broth, and then carrying out purification processing such as chromatography, crystallization or filtration purification to meet the aimed purity.

On the other hand, the procedures of synthetic chemistry are usually more difficult and tedious. This is because of (i) the removal of residual toxic solvent, (ii) the formation of more complex mixture of chemical by-products and synthetic impurities.

Downstream processing of fermentation-based production is not without its challenges. Indeed, one of the challenges is the relatively poor stability of the PQQ-rich fermentation broth. If left unprocessed, PQQ may degrade or convert at a fast rate, affecting the yield and purity of the final product, if left unprocessed. This instability mandates proper harvesting and early-processing techniques to stabilize the product. 

Leading Chemical is a high-tech enterprise specializing in the R&D, production and sales of new food ingredients, functional food ingredients and natural plant active ingredients. Our company is committed to offering healthy and safe raw materials for dietary supplements to global consumers. The produced PQQ disodium salt is content and purity over 99%, more active materials and better effects after absorbed by the body, and has got various certificates. Any needs feel free to reach out to us.

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