【Ten Years of Great Development in Chemical Equipment】From 1992 to 2013, the technology for producing succinic acid via fermentation enabled pilot-scale production of succinic acid

Decoding the codes of biological methods: Succinic acid is an excellent platform compound with wide applications in the fields of chemistry, materials science, pharmaceuticals, and food industry. It has been listed by the U.S. Department of Energy as one of the 12 most valuable platform compounds for the future. However, at present, the production of succinic acid relies mainly on chemical synthesis routes using petroleum-based benzene as raw material, making it a low-end industry characterized by high energy consumption, high material consumption, high water usage, and high pollution. 　　Developing green bioproduction technologies for succinic acid allows for reduced dependence on petroleum resources, lowers the production costs of succinic acid, minimizes environmental pollution, and enables green and sustainable development; this is currently a key focus in the development of the international biotechnology industry. Internationally, companies such as DSM in the Netherlands, Myriant and Bioamber in the United States, BASF in Germany, and Mitsubishi Chemical in Japan have developed biomanufacturing technologies for producing succinic acid through microbial fermentation. 　　In January 2010, Zhang Xueli, who had worked at the University of Florida in the United States for over 4 years, returned to China to undertake research on green bioproduction technologies for succinic acid. By mastering the entire set of techniques in systems metabolic engineering, Zhang Xueli’s research team used Escherichia coli as the starting strain, combined rational modification of the succinic acid synthesis pathway with evolutionary metabolism of the strain, and quickly developed an E. coli cell factory for the efficient production of succinic acid. 　　“The key to making progress is to improve succinic acid production capacity by combining rational modification with evolutionary metabolic techniques. During the evolutionary process, a series of entirely new key mutations were discovered; these mutations can enhance the supply of reducing power in cells, thereby increasing the rate of conversion of succinic acid into sugar acids ； On the other hand, many rate-limiting enzymes in the succinic acid synthesis pathway are activated, thereby increasing the yield and production rate of succinic acid. ”Zhang Xueli told a reporter from China Science News. 　　By comprehensively considering the energy supply, precursor supply, and redox balance in the succinic acid synthesis pathway, the research team designed the optimal synthesis route, enabling the sugar-to-succinic acid conversion rate to approach the theoretical maximum (1 ton of glucose can produce 1 ton of succinic acid). Compared with existing foreign technologies, it has a significant advantage in terms of conversion rate.

To ensure a continuous supply of resources, the eighth day of the first lunar month in 2013 was the first working day after the Spring Festival, and Zhang Xueli saw the general manager of Landian Biology Company waiting at the entrance of the Tianjin Institute of Industrial Biology. 　　Previously, the company had held several rounds of negotiations with Zhang Xueli. During this face-to-face meeting, Landian Biology demonstrated sufficient sincerity. At that time, several companies were competing to acquire the technology for producing succinic acid via fermentation from the Tianjin Institute of Chemical Technology. 　　“Industrial biotechnology is developing rapidly, and from the perspective of resources and the environment, this technology offers significant advantages. The same is true on an international scale: as soon as such technologies emerge, a number of companies immediately start to pursue them. ”Zhang Xueli said that it is estimated the future market potential for succinic acid will exceed 2.7 million tons per year, with an annual value of 16 billion US dollars. 　　Zhang Xueli possesses experience in industrialization; the fermentation method he developed for producing L-alanine was transferred to Anhui Huaheng Bioengineering Co., Ltd., where industrial production of this substance was achieved for the first time on an international scale. Therefore, he has his own considerations when choosing partners for the commercialization of achievements: first, the company truly wants to scale up its operations ； Second, strong economic strength ； Third, there is relevant production experience. 　　Landan Biology’s parent company is one of the top three enterprises in China’s edible alcohol industry, and it is listed on the NASDAQ in the United States. Due to the meager profits from edible alcohol, companies are in urgent need of achieving transformation and upgrading. 　　“This is the most sincere partner in terms of cooperation, and they also have the courage to take action. ”Zhang Xueli said that the two parties ultimately reached a cooperation agreement in March 2013. In May, the laboratory pilot test was completed in a 200-liter fermenter at Tianjin Gongsheng Institute, and it was accepted by Landian Biology. Subsequently, the company established a pilot production line, and pilot testing began in October. Two months later, the pilot test was successful. The rapid and efficient execution capability of private enterprises has accelerated the industrialization process significantly. 　　The company plans to build an industrial production line for succinic acid with a capacity of 10,000 tons this year, and subsequently expand it to an industrial production line capable of producing 500,000 tons of succinic acid per year as well as 100,000 tons of PBS plastic per year. Upon completion, the annual operating revenue is expected to reach 9.34 billion yuan. 　　The biological production of succinic acid allows for reduced reliance on petroleum resources, helps to save energy and reduce emissions, and simultaneously promotes the use of biomass agricultural products. Furthermore, the biological method can absorb one mole of carbon dioxide for every mole of succinic acid produced, which greatly contributes to improving economic efficiency. This is also one of the reasons why companies are pursuing industrial biotechnology.

Driving force for industrial upgrading: Developing technologies for fermenting non-grain biomass feedstocks to produce succinic acid can reduce the production costs of succinic acid as well as those associated with the manufacturing of PBS plastics, thereby facilitating the wider use of PBS plastics. Therefore, the production of succinic acid is merely the first step in the company’s transformation plan; Landian Biology is targeting PBS plastics as a promising industry. 　　The polymerization of succinic acid and 1,4-butanediol yields PBS (polybutylene succinate) plastic, which is a biodegradable plastic with excellent properties. Replacing existing petroleum-based plastics with PBS plastics is key to addressing white pollution and promoting industrial upgrading. 　　However, despite years of promotion for PBS plastic, little progress has been made. Even the companies that invested in this area are reluctant to produce, as they incur losses and gain no recognition from it; “currently, the PBS market in China is less than 10,000 tons.” Zhang Xueli believes that the difficulty in promoting PBS plastics is mainly due to the high costs of its precursors, succinic acid and 1,4-butanediol. 　　Through biological methods for the production of succinic acid, the production cost per ton has dropped to 10,000 yuan, compared with 14,000 yuan under chemical methods. “The production cost per ton needs to be reduced below 8,000 yuan in order to overcome the current price barrier to replacing PBS in the market. ”Zhang Xueli expects that this cost target can be achieved in about 3 years. 　　Fully tapping into the potential of microorganisms to develop advanced biomanufacturing technologies that feature low energy consumption, low material usage, and low pollution is the essential path for the upgrading of traditional manufacturing industries. 　　Regarding the role that research institutes should play in the process of industrial upgrading, Zhang Xueli believes that it is necessary to first select projects with potential for industrial application; \"once these are determined, the goal in terms of technological development is to create the best technology in the world.\" 　　Just as with the technological transfer for producing succinic acid via fermentation, Zhang Xueli never took the initiative to approach companies for industrialization of his research findings. “Rather than spending time looking for companies and telling them how great the project is, it’s better to focus on conducting research; even if the technology isn’t the best, it will still be among the best, and the companies will come to you on their own. ”Zhang Xueli emphasized the need to trust the power of the market, as companies have their own judgment regarding technical metrics. 　　However, to develop the best technologies, researchers need to continuously improve their technical skills and fundamental research capabilities. Zhang Xueli admitted that his basic research capabilities are a weakness, and there is still a gap compared to the best researchers in the world; \"They carry out a lot of original research, and even research of an applied nature can result in papers being published in journals such as Nature and Science.\" 　　All chemicals are produced using biotechnology, and breaking free from oil dependence is a shared dream around the world. However, the bulk chemicals that can currently be replaced through industrial biotechnology are “countable on one’s fingers.” More fundamental and original research needs to make breakthroughs, and Zhang Xueli believes this is of vital importance, requiring interdisciplinary collaboration. And every breakthrough will drive industrial upgrading and economic development. 　　(Originally published in China Science News, Page 7, January 14, 2014; adapted)

【Ten Years of Rapid Development in Chemical Equipment】Pilot-scale testing completed for the process of producing succinic acid via the aqueous-phase catalytic hydrogenation of maleic anhydride from 2013 to 2023 https://bbs.hcbbs.com/thread-5498395-1-1.html (Source: Haichuan Chemical Industry Forum Website)

【Ten Years of Rapid Development in Chemical Processing Equipment】The World’s First Pure Hydrogen Vertical Furnace Demonstration Production Line, 1303–2022. Pure Hydrogen Vertical Furnace: https://bbs.hcbbs.com/thread-5498428-1-1.html (Source: Haichuan Chemical Industry Forum Website)

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