June 16, 2024

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CO2-based biomanufacturing: Challenges from basic research to industrial applications

CO2-based biomanufacturing: Challenges from basic research to industrial applications


CO2-based biomanufacturing: Challenges from basic research to industrial applications.


Brief Instroduction

In the past few decades, great efforts have been made in carbon dioxide (CO 2 ) capture and utilization, but the large-scale utilization of CO 2 through biotechnology is still lacking market competitiveness, and new solutions and technologies are urgently needed. 

Scientists recently reviewed the progress and challenges in biofixation of CO2 in third-generation (3G) biorefinery technologies, with implications for raw materials, carbon fixation pathways and the key factors involved , energy Supply and their efficiency in assimilating CO2 into biomass, and subsequent 3G-based products are excellently summarized and discussed.

The paper also introduces the prospect of 3G biorefinery, points out the existing challenges, and provides forward-looking suggestions for future development.

The article also discusses the opportunities and challenges of integrating multiple carbon fixation pathways and techniques from chemical, biological, and process engineering to achieve closed-loop CO fixation and utilization.

In addition to the technical aspects, the article also highlights the need to further increase social, political and economic incentives.


This review briefly introduces the main contents, and further discusses several issues of concern for CO2-based biomanufacturing from basic research to industrial applications:


① Mechanism of carbon-carbon bond generation at atomic and molecular levels Conduct more in-depth basic and quantitative research to significantly improve the efficiency of key enzymes and metabolic modules of the carbon fixation pathway;

② Conduct systematic quantitative research on the interaction between carbon fixation reactions and metabolic networks at the metabolic pathway and cellular level;

③ In the biorefinery sense, physical, chemical, and electrochemical CO capture and conversion methods are combined with biological processes, while downstream processing for product recovery is considered;

④ From the perspective of industrial applications, biosynthesis-based autotrophic There are multiple technical bottlenecks and economic constraints in manufacturing, which are difficult to solve in the short term, and mixed trophic biosynthesis (using CO2 and mixed carbon sources) is a practical solution;

⑤ Most CO2The fixation pathway and its products are still in the “proof-of-concept” stage, and more engineering research is needed to achieve the technology needs from “0 to 1” to “1 to 100” to truly contribute to carbon neutrality.

CO2-based biomanufacturing: Challenges from basic research to industrial applications


Main contents


One of the greatest challenges facing humanity in this century is the energy transition and climate change, both of which are closely related to the emission and use of carbon dioxide (CO 2 ). Forced by the public’s high attention to frequent extreme climates and strong public opinion pressure, major industrial countries in the world have announced or even advanced the time points for carbon peaking and carbon neutrality.

In particular, China’s recent major measures in this regard have proposed to strive to reach the peak of CO 2 emissions by 2030 and achieve carbon neutrality by 2060, making the reduction, capture and utilization of CO 2 a major issue in various fields. urgent task.

In order to achieve the above goals, fundamental changes in industrial technology and relevant national industrial policies are required to transform the energy system from fossil energy to renewable energy, and the manufacturing industry from non-renewable carbon resources to renewable carbon resources.

CO2-based biomanufacturing is the best way to achieve both goals in the long run.


CO2-based biomanufacturing is also often referred to as third-generation biorefinery technology in the literature to distinguish it from the first-generation biorefinery technology that mainly uses starch and other sugar-containing substances as raw materials and biorefinery technology based on lignocellulose and other raw materials.

The second-generation biorefinery technology using substances as raw materials is characterized by using microorganisms and algal cell factories to convert carbon-one compounds such as CO2 into bioenergy, chemicals and materials under the drive of renewable energy such as light or electricity .

In principle, biomanufacturing has the advantages of easy mass production, mild conditions, good selectivity, and environmental friendliness. It conforms to the concept of green ecology. In recent years, biomanufacturing based on CO2 has received extensive attention.

Professor Tan Tianwei’s group from Beijing University of Chemical Technology and Professor Jens Nielsen’s group (Sweden/Denmark) co-authored the review article “Third-generation biorefineries as the means to produce fuels and chemicals from CO 2 ” published in Nature Catalysis (Liu et al , 2020 ) summarizes the research on CO 2 fixation by biological methods over the years , and systematically introduces the third-generation biorefinery based on CO 2 from four aspects: feedstock, carbon fixation pathway, energy utilization and products.

This review article is detailed and rich in content. It not only sorts out a large number of related literatures, but also points out the difficulties and key points of CO 2 -based biomanufacturing, and puts forward useful suggestions and prospects.

This article briefly introduces this review article, and puts forward some views and suggestions from the perspective of basic research and engineering application based on my own related research, which is intended to attract new insights.


Liu et al. pointed out that the anthropogenic CO 2 emission is as high as 33 billion tons per year, and its sources are very wide, such as industrial production waste gas, landfill waste gas, biomass gasification, vehicle and respiratory emissions. CO2 from different sources contains different impurities, such as nitrogen oxides and sulfur oxides, and the tolerance of host microbial cells to impurities will be one of the important factors affecting biorefinery.

For another example, the temperature of industrial flue gas is very different from the temperature of biological fermentation.


Cooling the flue gas will cost a lot, and temperature tolerance will also be one of the indicators to test the host microorganism. The author believes that how to comprehensively utilize the energy of high-temperature gas to provide energy for biosynthesis or even recover energy as downstream products is worth further exploration, such as using temperature to make CO 2 react with a substance to generate active substances for biosynthesis and recycling.

Theoretically, CO 2 can react with epoxides to form cyclic carbonates at high temperature. If it can be recycled through biological or chemical reactions, it can reduce the activation energy of CO 2 . In addition, the combination of biological and physical methods can be considered.

The standardized pretreatment of CO2 in the physical method will improve the stability of biosynthesis, and the use of CO2 compressed gas to establish a high-pressure CO2 bioreactor will be beneficial to the relevant enzyme reaction equilibrium. Compositing direction moves.


In terms of carbon sequestration pathways, Liu et al.’s article systematically analyzed and elaborated 8 known CO 2 biological carbon sequestration pathways (Figure 1), including 6 natural carbon sequestration pathways, namely the Calvin-Benson-Bassham cycle (Calvin-Benson-Bassham cycle). cycle, CBB cycle), Wood-Ljungdahl pathway (also known as reductive acetyl-CoA pathway, reductive acetyl-CoA pathway), dicarboxylate/4-hydroxybutyrate (DC/HB) cycle , 3-hydroxypropionate/4-hydroxybutyrate cycle [3-hydroxypropionate/4-hydroxybutyrate (HP/HB) cycle], 3-hydroxypropionate double cycle (3-HP bicycle) and reduced tricarboxylic acid (TCA) pathway (reductive TCA cycle), and 2 artificially designed and proven carbon fixation pathways, namely reductive glycine pathway (rGlyP) and crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA Cycle [crotonyl-coenzyme A(CoA)/ethylmalonyl-CoA/hydroxybutyryl-CoA, CETCH cycle].

The Calvin cycle is a natural pathway for plants and algae to fix carbon dioxide, and its key enzymes are
D-ribulose-1,5-bisphosphate carboxylase/oxygenase, D-ribulose-1,5-bisphosphate carboxylase/oxygenase,

RubisCO), the catalytic efficiency of this enzyme is very low, only a few molecular reactions can be catalyzed per minute, and there have been no good success stories for the modification of this enzyme for many years.

The dicarboxylic acid/4-hydroxybutyric acid cycle, the 3-hydroxypropionic acid/4-hydroxybutyric acid cycle, and the 3-hydroxypropionic acid dual cycle are naturally present in some autotrophic microorganisms and are activated by thiamine pyrophosphate (ThDP) The latter carbonyl carbon or the active carbonyl α -carbon acts as an acceptor to fix CO2. Cleavage of acetyl coenzyme A or pyruvate is the overflow product.

The energy consumption of carbon fixation reaction in these natural pathways is relatively high, which is difficult to apply in practice.

The reduction of tricarboxylic acid pathway can be regarded as the reverse reaction of the tricarboxylic acid cycle, which can fix two molecules of carbon dioxide and overflow one molecule of acetyl-CoA.

This pathway can be driven by high-pressure carbon dioxide and is expected to become one of the focuses of follow-up research.

The article also introduces three theoretically designed CO2 carbon fixation pathways, such as the malonyl-CoA-oxaloacetate-glyoxylic acid (MOG) pathway, etc., the final spillover product is glyoxylic acid through a two-step carbon fixation reaction; The number of reaction steps and theoretical energy utilization efficiency are better than those of the above-mentioned natural pathway.

However, the carbon fixation reaction from coenzyme A to pyruvate in the pathway still has a high energy barrier.

Whether the reaction can be completed efficiently still needs to be further verified by experiments. In contrast, the CETCH cycle was designed artificially to avoid CO2 fixation by coenzyme A , and utilized NADH such as crotonyl-CoA carboxylase/reductase to fix CO2 to lower the energy barrier, enabling a multi-step cascade. The reaction can be successfully completed in vitro, but its in vivo feasibility remains to be further confirmed.

Different from the above-mentioned fixation of CO2 through cyclic reactions , the Wood-Ljungdahl pathway and the reduced glycine pathway fix CO2 through linear reactions, which are less dependent on or interfere with central metabolism, and we believe that from the high required for industrial applications From a flux perspective, this may be the unique advantage of these two pathways.

In general, the current research on the interaction between carbon dioxide fixation reaction and metabolic network is still very limited, and it has important scientific research value for the reconstruction and systematic quantitative analysis of its interaction network (including regulatory network), which deserves attention.


CO2-based biomanufacturing: Challenges from basic research to industrial applicationsFig. 1 Schematic diagram and main features of six natural and two artificially constructed CO 2 fixation pathways (CETCH cycle and rGlyP)


(In addition to CO 2 and HCO 3 − , formic acid can also be seen as a molecular carrier for CO 2 fixation, the spillover metabolites and key enzymes of each pathway are highlighted in color; in addition, the consumption of each pathway is also given. ATP and reducing equivalents, the number of enzymes involved.

The GCS system in the reduced glycine pathway is used as an example to demonstrate the complexity of its core carbon fixation mechanism and the need for in-depth research.

MCR—malonyl-CoA reductase; 4-BUDH— 4-hydroxybutyryl-CoA dehydratase; PCS—propionyl-CoA synthase; ACLY—ATP-citrate lyase; KOGR—2-oxoketoglutarate synthase; CCR—crotonyl-CoA carboxylation/ Reductase; FDH—formate dehydrogenase; RuBisCo—ribulose-1,5-bisphosphate carboxylase/oxygenase; GCS—glycine cleavage system; CODH—carbon monoxide dehydrogenase)


The article by Liu et al. analyzed the advantages and disadvantages of each pathway, energy sources, substrates and products, key enzyme types and enzyme activities.

In particular, the article points out that the key factors in the practical application of carbon fixation pathways are oxygen sensitivity, ATP demand, thermodynamics, enzyme kinetics and CO 2 utilization form.

Oxygen sensitivity is linked to ATP requirements and closely related to subsequent product requirements, thermodynamics is linked to the ratio of intracellular NAD(P)H/NAD(P), enzyme kinetics determine the rate of cell growth, receptors are linked to CO 2 In itself or its bicarbonate form combined affects the efficiency of carbon sequestration and the optimization of conditions.

The author believes that one of the main differences between different carbon fixation pathways is the utilization efficiency of ATP. After carbon dioxide is fixed, a carboxyl group is often obtained, and the activation of the carboxyl group and the conversion of subsequent functional groups often require consumption of ATP.

Wood-Ljungdahl pathway, reduced TCA pathway, reduced glycine pathway and CETCH cycle consume less energy, while Calvin cycle, DC/HB cycle, HP/HB cycle and 3-HP double cycle all consume more ATP (Fig. 1). How to avoid the consumption of ATP is one of the important factors in constructing an efficient carbon fixation pathway.

Therefore, it is necessary to conduct more in-depth and basic research on the carbon fixation pathway, such as the mechanism of the core carbon fixation enzyme on the binding and transport of small molecules, which is Key issues for improving carbon sequestration efficiency and constructing new approaches.

The chemical nature of the carbon fixation reaction is a nucleophilic attack reaction, and the nucleophilic group carries electrons to attack the electropositive carbon atom in CO2 to form a carboxylic acid or its derivatives .

Since the carbon atoms in CO 2 are already in the stable structure of octet and have strong kinetic inertness, the nucleophilic attack needs to overcome a higher activation energy to complete, which requires the nucleophile itself to be in a relatively active high energy Therefore, carbon fixation enzymes often have elaborate and unique mechanisms of action.


Taking the reduced glycine pathway as an example, its core carbon-fixing enzyme is the glycine cleavage system (GCS), which can reversely synthesize glycine using CO 2 , 5,10-methylenetetrahydrofolate and ammonia (NH 3 ). Simultaneously immobilize 2 molecules of one-carbon compounds (CO and formic acid) and 1 molecule of ammonia (Figure 1).

The glycine cleavage system is a multi-enzyme complex composed of three enzymes (P protein, T protein, L protein) and a carrier H protein.

The lipoyl lysine arm on the carrier H protein is used as an active nucleophile to accept and transfer CO 2 .

The reduced glycine pathway is considered to be one of the most advantageous pathways in the carbon fixation pathway, with fewer reaction steps, lower ATP requirements, better tolerance to oxygen by enzymes in the pathway, and less interference with central metabolism. good potential for industrial applications.

Recently, the reduced glycine pathway has been successfully expressed in microorganisms such as E. coli , Saccharomyces cerevisiae , and Clostridium drakei , enabling host cells to synthesize primary metabolites such as organic acids and amino acids using formic acid and CO 2 .


However, if formic acid and CO 2 are simply used as carbon sources, the cell growth is very slow, and it is difficult to meet the requirements for industrial microorganism hosts.

One of the main reasons is that the understanding of the core mechanism of carbon fixation is far from enough: the interaction between the components of the glycine cleavage system, the three forms of the lipoylation carrier H protein ( Hox , Hred , Hint _), its self-protection and deprotection, the synthesis of lipoyl lysine arms, the way of carrying carbon-one unit (metabolic channels), and the influencing factors, all lack systematic and quantitative analysis, hindering the engineering research of GCS and optimization, let alone redesigning and transforming it by means of synthetic biology.

Recently, we performed molecular dynamic dynamics simulations on the self-protection and deprotection process of H protein, revealing the process of H int deprotection induced by T protein from the atomic level, and found several stages in the release process of aminomethyl group.

The mutation of the corresponding key amino acid residues can significantly increase or decrease the activity of the GCS system, which provides a quantitative theoretical basis for the rational regulation of rGlyP.

There have been many reports on the Wood-Ljungdahl pathway in the literature, but the binding of carbon monoxide (CO) and the binding of CO 2 in a number of coenzyme A-dependent carbon fixation pathways also require more in-depth quantitative research.

The same is true for other approaches. The expression and application of these biological carbon fixation pathways in heterologous microorganisms, especially industrial microorganisms, are still in their infancy, and have shown their difficulties and limitations, requiring comprehensive structural biology, computational biology, and machine learning.

Multidisciplinary research on synthetic biology, biochemistry and metabolic analysis. In addition, the transformation of new metabolic pathways based on the original CO 2 fixation reaction is also of great scientific and practical value.

For example, Bouzon et al. introduced exogenous transaminase and aldolase into the homoserine metabolic pathway, so that it can be cleaved into pyruvate and formaldehyde, realizing a new one-carbon metabolic cycle, the interaction between CO 2 fixation and one-carbon metabolism. It is also one of the focuses of future research.


Recently, Science magazine published an article titled “Cell-free chemo-enzymatic starch synthesis from carbon dioxide” by Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences.

After 6 years of hard work, the researchers finally successfully synthesized starch by chemical-enzyme cascade conversion using CO 2 in vitro, and its efficiency can reach 8.5 times that of plant natural starch under specific conditions.

This pioneering work provides a theoretical basis for the realization of soilless food production in the future, and has important academic value and potential great social significance. This work constructed 4 cascade conversion modules, namely the C activation module of CO2 to formaldehyde, the C3 condensation conversion module of formaldehyde to glyceraldehyde 3-phosphate, and the C6 conversion module of glyceraldehyde 3-phosphate to glucose 6-phosphate . modules and finally the C n modules of polymerized synthetic starch .

The process of carbon fixation is that CO 2 and hydrogen synthesize methanol under the action of metal catalyst, methanol is catalyzed by enzymatic oxidation to obtain formaldehyde, and 3 molecules of formaldehyde are directly condensed into three-carbon compounds under the action of formolase (fls).

The fls that catalyzes the condensation of formaldehyde was transformed from benzaldehyde condensase by American scientists through computer rational design in 2015. It has attracted much attention because it can directly condense 3 molecules of formaldehyde, but its activity has been very low, resulting in the accumulation of formaldehyde and toxicity. Seriously limit its further application.

Researchers  successfully transformed fls, which increased its vitality by 4.7 times, greatly reduced the accumulation of formaldehyde, improved the synthesis flux, and broke through the key bottleneck of C 1 synthesis.

It is expected that, based on the synthetic modules constructed in this work, there will be theoretically many more compounds that can be derived from COIt is synthesized, which greatly promotes the development of C 1 biosynthesis.

While we are glad to achieve a breakthrough from 0 to 1, we should also see the difficulties and challenges in the process of realizing industrialization (1 to 100) in the future. In vitro large-scale biosynthesis of a multi-enzyme system involving up to 14 enzymes (including cofactor and by-product cycles) faces many difficulties. Utilization is not yet mature; enzyme dosage, stability and cost control, industrialized C 1 synthesis reactor, product separation and purification, are all difficult problems to be solved in industrialization.


In terms of energy utilization, since CO 2 is the final product of the combustion and oxidative metabolism of energy compounds, its energy is the lowest, and external energy must be introduced to utilize CO 2 (Fig. 2).

The article by Liu et al. discusses three types of carbon sequestration methods based on energy sources: photoautotrophic synthesis, chemoautotrophic synthesis, and electroautotrophic synthesis.

Photoautotrophic synthesis mainly exists in plants, algae and green sulfur bacteria, etc., and utilizes photons of different energies and quantities through the Calvin cycle, the 3-hydroxypropionic acid double cycle and the reductive TCA pathway. In recent years, photoautotrophic synthesis has been transplanted into model microorganisms such as E. coli or yeast, but is still in its infancy.

The main limiting factors for photoautotrophic synthesis are the low collection efficiency of light energy and the high requirement of optical density for microbial growth.

Chemical autotrophic synthesis mainly means that host microorganisms can use electron-donating chemicals to obtain energy, such as hydrogen, CO, formic acid and metal minerals. The author believes that although reducing metal minerals can be used as energy donors, the source range is Relatively narrow, not in line with the large-scale utilization of CO2 .

Electroautotrophic synthesis is the use of electrical energy to directly or indirectly provide energy to host cells, in which the indirect method is similar to chemical autotrophic synthesis, using electrical energy to electrochemically reduce CO2 to CO or formic acid and then be utilized by cells.


The author believes that with the rapid development of photovoltaic cells in the world, especially in some countries, the overall energy utilization efficiency is likely to be high by converting light energy into electrical energy through photovoltaic cells, and then performing direct or indirect electroautotrophic synthesis.

Compared with the traditional photoautotrophic synthesis, the utilization of hydrogen, CO, and formic acid as carbon sources and energy sources for biological fermentation has great application potential, which is also one of the advantages of the Wood-Ljungdahl pathway and the reduced glycine pathway.

At present, although the direct use of electrical energy for biosynthesis has attracted great attention, its efficiency is extremely low, and the mechanism is still unclear.

Microorganisms reported in the literature such as Clostridium pasteurianum) directly from the electrode for biosynthesis, there is no direct evidence, it is likely to be an artifact caused by electron transfer intermediates such as hydrogen through the electrode surface.

From the existing literature, indirect via hydrogen and formic acid may be a more realistic electrochemical CO bioavailability pathway, especially formic acid may be a more attractive energy carrier under aerobic conditions.

The article points out the key influencing factors of electroautotrophic synthesis, including the choice of host, the solubility and mass transfer rate of the energy carrier, the concentration of CO in the electrolyzer, and the compatibility of electrodes and microorganisms.

The author believes that in further research, the analysis of the electron transfer mechanism of the electronucleophilic host and the engineering research of the electronucleophilic host as a model chassis cell are particularly worthy of attention. Compared with light energy, electricity can achieve a higher energy density.

Using light energy to generate electricity and then use electric energy to ferment is an effective strategy to improve energy density.

In addition, electric energy can also be converted from wind energy and nuclear energy.

The UHV transmission with Chinese characteristics solves the problem of electric energy transfer, so that electricity can be used as a standard high-efficiency raw material to participate in the carbon sequestration pathway.


CO2-based biomanufacturing: Challenges from basic research to industrial applications
Figure 2 CO2-based biomanufacturing : from “proof of concept” to large-scale industrial application


From the perspective of practical industrial application, it is necessary to solve the key bottlenecks in pure autotrophic synthesis, such as mass transfer limitation of substrates, limited supply of energy (ATP) and reducing equivalents, slow cell growth and low product formation rate, mixed nutrients ( mixotrophy) biosynthesis is an effective solution.

Mixotrophy, which involves the co-utilization of one-carbon compounds (C 1 ) and organic substrates as a combination of heterotrophic and autotrophic biosynthesis, has been relatively poorly studied. Scientists (2021) introduced and discussed the different pathways of C1 – mixotrophy and their potential, and demonstrated their advantages with examples.

Another possibility for mixed trophic biosynthesis is to improve the utilization of C1-fixed apoplastic reactions that are naturally present in heterotrophs .

Reconstruction of carbon metabolism can lead to forced C fixation into the final product, thereby overcoming the inherent limitations of the product yield achievable by heterotrophs.

In the short to medium term, the use of natural or synthetic pathways for C1 fixed modules in mixed nutrition represents a promising and viable strategy for bioprocesses.

To this end, more quantitative and systematic studies of the intracellular interactions of C1 fixation and catabolic modules are required. Possible catabolite inhibition or other interfering natural regulatory mechanisms in mixed nutrition should be better investigated.

Step-by-step engineering of established production strains is a necessary effort to increase the industrial relevance of C1 feedstock -based biosynthesis.


The bottlenecks in large-scale green biomanufacturing lie in constraints on the sustainability and price of raw materials, production costs, and product extraction. Realizing the biological utilization of C 1 raw materials represented by CO 2 is the best way and key technology to solve the source of raw materials.

Synthetic biology has made great achievements in improving the conversion rate of C 1 raw materials and reducing the cost. At present, the production cost of third-generation biorefinery technology is generally too high, and there is still too little work on product separation and extraction. The article by Liu et al. finally summarizes from the product aspect.

Currently, the third-generation biorefinery can synthesize a variety of fuels and chemicals, and some of them have begun to enter the stage of commercial application, such as the use of steelmaking waste gas to produce fuel ethanol, and the use of microalgae to synthesize fatty acids. compound.

The article has made a rich survey and summary of the latest technologies and information on C 1 biosynthesis, and made an outlook on C 1 biosynthesis.

The follow-up worthy of our continued consideration are: as mentioned in the cited literature, the use of biomass to synthesize hydrogen and generate electricity, The price of electricity can be reduced to 2 cents/kWh, while the C1 biosynthesis goal is to use electricity and C1 compounds to synthesize biomass, it is difficult to say that such electricity applications will be more efficient, and use in situ ( in situ ) light or The technology research and development of the fusion of electric water hydrogen production and artificial photoelectric driven CO 2 reduction and biosynthesis is expected to make major breakthroughs and influential work in this research direction.


In terms of industrial applications, the vast majority of carbon sequestration pathways and products are still in the “proof of concept” stage, which is a breakthrough from “0 to 1” for a single compound, and its technical indicators KPI (key performance indicators) are far from large-scale. Biomanufacturing needs (Figure 2).

For the industrial bio-manufacturing of bulk chemicals, the product concentration is often required to be in the hundreds of grams per liter (about 100 g/L), and the production intensity is above 2 g/(L·h).

Except for individual processes and products, CO 2 autotrophic biosynthesis can usually only reach the concentration level of mg and g/L, and the production intensity is below g/(L·d).

In the foreseeable future, achieving a CO2-based large-scale biomanufacturing process from “0 to 1” to “1 to 100” will also require breakthroughs in engineering technology combined with original process technologies.


From the history of industrial development, from basic science to the formation of industries, breakthroughs in engineering technology or original process technologies are crucial.

One of the revolutionary achievements of the chemical industry at the beginning of the 20th century—the artificial synthesis of ammonia—is a model of the combination of science and technology.

It was done in collaboration with a team led by Prof. Fritz Haber from the Karlsruhe Institute of Technology in Germany and Dr. Karl Bosch from BASF AG.

In fact, the conditions [1020 °C, 1 bar (1 bar=10 5 Pa)] and the results obtained by Haber in his research on the principle of the process (the yield of ammonia around 1904 is about 0.005%) are far from being industrialized. Yes, it was BASF’s breakthrough in high-pressure chemical processes and equipment that spawned the world’s first high-temperature and high-pressure (about 450 °C, 300 bar) chemical reactor, which enabled the industrialization of this process in 1913, resulting in The Agricultural Revolution, for which they were awarded the Nobel Prize in Chemistry in 1918 and 1931, respectively.

It can be said that without this close integration of science and engineering, it is difficult to produce such an epoch-making technology! CO2-based biosynthesis also requires innovation in bioreactors.

Unlike traditional biosynthesis, it is a volume-reduced reaction process, coupled with low gas solubility, high-pressure biosynthesis has obvious advantages, but research in this area is extremely few.

Recently, Steffens et al. found that in the bacterium Hippea martima , the synthesis of pyruvate from CO and hydrogen can be achieved by reversing the TCA cycle simply by increasing the ambient CO concentration or partial pressure (40%).

In this process, there is no need for enzymes other than the tricarboxylic acid cycle enzyme system to participate in the reaction, as long as the citrate synthase has a higher expression level.

This phenomenon may exist in many other organisms and is mainly determined by thermodynamics. This provides a good biological theoretical basis for high – pressure CO biotransformation.


The biotransformation and industrial application of one-carbon compounds (C 1 ) represented by carbon dioxide, methane, formic acid and methanol is a major opportunity and challenge for synthetic biology and green bio-manufacturing, and a major issue to help carbon neutrality.


The research focuses on the comprehensive application of synthetic biology, process systems engineering, materials science and other basic sciences and technologies, realizing the organic integration of one-carbon biotransformation, photoelectric biotechnology and engineering processes, and finally realizing the utilization of atmospheric CO 2 and solar energy and other green Energy is bio-manufactured and contributes to human mitigation of climate change.




CO2-based biomanufacturing: Challenges from basic research to industrial applications

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