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2023-12-21 08:41:10 | onclick: | Vitamin C synthesis, from "two-step completion" to "one step in place"

In the vast vitamin family, the most familiar is probably vitamin C.
As one of the essential vitamins of the human body, vitamin C is widely used in various fields such as medicine, food, cosmetics and feed because of its strong antioxidant ability, free radical removal ability and other related physiological functions.According to statistics, the annual global vitamin C demand is about 220,000 tons, more than all other vitamin products combined, and is still growing at a rate of about 10% per year.
However, what many people do not know is that vitamin C, which has the largest "mass base", is the most complex synthesis process of almost all vitamins of the same type.This deficiency also greatly restricts the development of the vitamin C industry.
Professor Zhou Jingwen of Jiangnan University's Center for Future Food Science has made important progress in the development of a step-by-step synthesis process for vitamin C, which has laid an important foundation for reducing energy consumption and cost.
Recently, relevant research has been published in Advanced Science and Biological Resources Technology respectively.
The most common vitamins are derived from the most complex methods.
Unlike many vitamins, vitamin C is an essential trace element of the human body, but the human body can not be synthesized naturally, only through external intake.However, overactive chemistry prevents vitamin C from remaining stable in complex liquid environments for a long time.
"That's why large-scale production of vitamin C is achieved in industry by synthesizing the precursor of vitamin C, 2-keto-L-guronic acid."Zhou Jingwen told the China Science Journal, but even the synthesis of this substance is complicated.
At present, the usual synthesis procedure of 2-keto-L-guronic acid is called the "three bacterial two-step method", that is, a specific type of fermentation microorganisms are added to sorbitol medium first to ferment it into sorbitol sugar.Two other fermentation microorganisms are then added to it, through this "mixed" fermentation system, to convert sorbitol into 2-keto-L-guronic acid.
"The reason why three fermentation bacteria cannot be added to sorbitol medium at the same time is that the latter two fermentation microorganisms can not only react with sorbitol, but also react with sorbitol to form other substances.This will greatly reduce the fermentation efficiency.Qin Zhijie, a member of Zhou Jingwen's task force and a postdoctoral fellow at Gangnam University's Future Food Science Center, explained.
However, the addition of additional fermentation steps will also reduce the efficiency of vitamin C synthesis and increase the cost of synthesis.Zhou Jingwen said, for example, each time before adding different fermentation microorganisms, the fermentation solution needs to be sterilized at high temperature, which means that the fermentation solution needs to be heated to 121 degrees Celsius in a short time."It's a time-consuming, energy-consuming and cost-effective process.”
In addition, one or two hundred tons of fermentation liquid needs to be transferred from one storage tank to another, a process that can take hours alone.
"As far as I know, the biosynthesis of vitamins other than vitamin C can almost be done in a single step, but only vitamin C, the most common vitamin, can be made using the most complex fermentation methods."The week said.
Achieving a "One-Bacterial Step"
The theoretical obstacles behind the complex synthesis of vitamin C have been well known in the industry since the 1990s, but they have not been broken for many years."So much so that anyone who claims to have successfully completed the 'one-step' fermentation of vitamin C would probably be considered a fraud."And the Lord said with a smile.
However, since 2006, after more than a decade of hard work, Zhou Jingwen team has actually achieved this goal.
In the study, the team successfully constructed a direct 2-keto-L-guronic acid fermentation engineering strain by introducing sorbitol dehydrogenase and sorbitol dehydrogenase, which can produce 61.8 grams of 2-keto-L-guronic acid per liter of sorbitol solution in 168 hours.
At the same time, the team also used structural biology to analyze the catalytic mechanism of sorbitone dehydrogenase, a key rate limiting enzyme in sorbitol fermentation, and increased its activity.
In order to solve the problem of vitamin C synthesis more quickly, the research team also studied the synthesis of vitamin C by one-step fermentation of glucose as the substrate.
Sorbitol, the original raw material for the synthesis of 2-keto-L-guronic acid, is obtained by glucose conversion."Our research aims to achieve direct conversion from glucose to 2-keto-L-guronic acid by developing a novel vitamin C synthesis process that omits the 'synthetic sorbitol' step."Qin Zhijie said that they have been able to achieve a 5-liter glucose fermentation tank, in 62 hours to achieve 2-keto-L-guronic acid production of 30.6 grams per liter, glucose conversion rate of 40%.
The "first chance" that should be taken.
Although remarkable results have been achieved in the field of vitamin C synthesis, Zhou's team's research has not stopped, and one of their current research focuses on the industrial application of the results.
"As the world's largest demand for vitamins, in the field of acidity alone, vitamin C is already the second largest acidity ingredient after citric acid, and its wide range of applications can be seen from this.""The week said.
According to customs statistics, in August 2023 alone, China's vitamin C exports reached 14,475.5 tons, an increase of 20%.
"The production of vitamin C also involves a large number of upstream and downstream industrial chain enterprises.This means that if it were not for us, but for other countries to make breakthroughs in vitamin C synthesis and significantly reduce the associated production costs, our industry would be severely affected.Zhou Jingwen said that according to estimates, if their results further improve efficiency and eventually industrialize, it will be possible to reduce the cost of vitamin C preparation by 50%.
It is worth mentioning that although the application field of vitamin C has been very wide, if the preparation cost is greatly reduced, its application range can continue to expand.
In the case of lysine, for example, when its production efficiency is low, people often choose to ingest it directly into the body, but with the improvement of lysine production efficiency, people began to add it to animal feed and supplement lysine.
Similarly, if vitamin C production efficiency and production are greatly improved, its use may also expand to aquaculture and other fields."We need to take the lead in this regard, " Mr. Zhou said.

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