Advanced Materials & (Bio) Processes

With the help of special enzymes and a biocatalytic method developed at the TU Hamburg, drugs could be produced in a more environmentally friendly and cheaper way in the future.

To understand the following process, we first need to look inside our body cells: each of them derives its energy from adenosine triphosphate (ATP). This is a substance that serves the body as an energy carrier and is therefore referred to as the basic energy building block of life. A person needs several kilograms of ATP per day. Yet the human body only contains between 50 and 200 grams of this substance. How is this possible?

When ATP is consumed, adenosine diphosphate (ADP) and a free phosphate are produced. This releases energy that the body can use. The ADP is then regenerated back into ATP. This requires new energy from food. This cycle takes place within a few seconds. At a biochemical level, ATP therefore provides energy that enables reactions to take place that would not be possible without this energy supply. This energy is transferred to the starting materials of the desired chemical reaction with the help of biocatalysts (enzymes).

Use for drug production

This is not only possible in nature, but also in factories. Many consumer goods are manufactured using chemical processes. The more efficiently and sustainably these can be realized, the better. This saves money and resources. Enzymes are a sustainable alternative to classic inorganic catalysts. Biocatalysis is primarily used in the industrial production of complex organic molecules. For example, in the production of pharmaceuticals. Some newly developed drugs are produced with the help of ATP. This is simpler and cheaper than traditional chemical synthesis. However, the provision of ATP is still very expensive.

A team led by Jan-Ole Kundoch, a doctoral student at the Institute of Technical Biocatalysis, has therefore developed a better regeneration system as part of a DFG project under the direction of Prof. Andreas Liese in the working group of Dr. Daniel Ohde and in collaboration with colleagues from Bioprocess Engineering at TU Dresden. Their newly developed so-called enzymatic cascade is more robust and less expensive than the previous procedure. The extremely inexpensive ethylene glycol, which is also used in antifreeze, is now used as the starting material.

Finding optimal reaction conditions

As part of the project, which ran for almost four years, it first had to be clarified whether the envisaged procedure was even biochemically possible. The next step was to improve it and bring it closer to industrial scalability. Two factors were particularly relevant here. The method had to work reliably and the costs had to be lower than for the previous procedure.

A total of five biocatalysts are now working together simultaneously. All of them have their preferred environmental conditions such as temperature, pH value, salt concentration, concentration of the respective starting material and product. The major challenge in Kundoch's project was therefore to find reaction conditions under which this system runs optimally. “We must have carried out 1,000 experiments,” reports Jan-Ole Kundoch, ”and initially examined all the biocatalysts individually and then built up the system piece by piece by adding one more biocatalyst at a time. In the end, I then examined and optimized the entire system.”

Kundoch sums up: “In this case, biocatalysis offers a good alternative to conventional chemistry, which often has to resort to toxic and environmentally harmful solvents that are used at high temperatures.” In addition to lower wage levels, less stringent environmental regulations are the reason why a large proportion of pharmaceutical production now takes place in India or China. The new ATP synthesis would therefore facilitate the political goal of producing more medicines in Europe again. At the same time, production costs would fall, which would relieve the burden on the healthcare system and make it possible to supply the world's poor population with essential medicines.

“Incidentally, in future it will be possible to produce substances in this way that cannot be synthesized chemically,” adds Kundoch. This means that completely new remedies can be invented.

Further information

You can find more information at TUHH Open Research

Chemical production processes often require a lot of energy and involve the use of environmentally harmful substances. A team at TU Hamburg is working on an alternative that essentially gets by with water, electricity and enzymes. 

The thing is reminiscent of a takeaway coffee mug. However, the lid does not have a simple drinking opening, but is studded with screws and tubes. And metal tubes protrude into the glass cup, vaguely reminiscent of straws."This is our 200-milliliter reactor," explains Victoria Bueschler, a doctoral student at the TU Institute of Technical Biocatalysis. "It can produce hydrogen peroxide and then react with other substances using enzymes." The idea: the new process should one day replace toxic and expensive chemicals in industry and also save energy.

Hydrogen peroxide (H₂O₂) is an important basic material for chemistry. Like water, it consists of hydrogen and oxygen - except that it has two oxygen atoms instead of one. This makes the molecule extremely reactive and an effective oxidizing agent, for example to bleach hair or convert hydrocarbons. "One example is the production of phenol from benzene," explains Bueschler. "Today, this requires high temperatures, toxic chemicals and expensive precious metal catalysts." If these catalysts could be replaced by enzymes, the reaction could take place under milder conditions - in other words, in a more environmentally friendly and energy-saving way. Bioelectrochemistry is the name of this still young, promising approach.

An electrode made of carbon

There are already enzymes that convert hydrogen peroxide into other substances as a reaction accelerator. However, if too much H₂O₂ is involved, it attacks the enzymes and checkmates them. It would be better if only as much hydrogen peroxide was present in the reaction as was needed at any given time.This is exactly what the TU team is aiming for in its "AIO-eChemBIO" project: The coffee cup reactor produces H₂O₂, which is immediately converted on the spot - a combination apparatus for production and synthesis. Hydrogen production takes place in a finger-thick rod that protrudes into the cup. "This is an electrode, it is essentially made of a special form of carbon," explains Bueschler's colleague Giovanni Sayoga, pointing to a deep black, ultra-light material. "This carbon has pores like a sponge. It consists of 90 percent air and is produced here at the TU." If this carbon sponge is placed in water and exposed to electricity, water molecules are split. This produces oxygen and hydrogen, which combine under suitable conditions to form hydrogen peroxide.

"All you really need is electricity and water and no additional chemicals," says Sayoga. The amount of hydrogen peroxide to be produced can be precisely adjusted via the applied current. And if the electricity comes from wind turbines and solar cells, production can be climate-neutral.

Follow-up project is already planned

The working group has already been able to show that the drinking cup reactor works in principle. However, there is still a lot of research work to be done before the process can be put into practice. For example: "Up to now, we have always had to refill the reactor after the reactions have run their course," explains Institute Director Prof. Andreas Liese. "In a follow-up project, we now want to try to make the process continuous." The bioelectrochemical reactor could then run day and night - an important prerequisite for use in industry. One day, such permanent reactors could then be modularly combined into larger units.
 
Victoria Bueschler and Giovanni Sayoga will soon have their doctoral theses in the bag. While Bueschler will remain at the institute as a group leader, Sayoga is toying with the idea of founding a start-up. "We have already sat down with a company that finds our project very interesting," he says. "Using our new process as a start-up for such a company would be an appealing idea."

More information

The activities in the "AIO-eChemBIO" technical biocatalysis project are embedded in the DFG priority program 2240 "eBiotech", in which research groups from all over Germany are working on the fundamentals of bioelectrochemistry.

More information: www.e-biotech.de/de/projekte.html

Researchers at TU Hamburg are producing climate-neutral energy sources from renewable raw materials such as wood residues and straw. The molecule lignin plays the main role here.

The bioeconomy is key when it comes to the future of the economy. It aims to solve global challenges by replacing fossil resources with various renewable raw materials. One fossil-free alternative, for example, is the molecule lignin. This is found in almost all plants and woody plants, such as grasses, shrubs and trees. Scientists at Hamburg University of Technology, supported by the TU Centre for Bio Based Solutions, are conducting research in the "ELBE - NH" consortium, which is funded by the Federal Ministry of Education and Research, to utilize lignin more efficiently for the bioeconomy.

Fertilizer for agriculture

In a plant on the TU Hamburg campus, an aqueous mixture is used to break down wood residues or straw into their basic components under high pressure and temperature. In addition to lignin, this also produces side streams, known as hydrolysates. The group of engineers from universities, research centers and industry has succeeded in producing lactic acid and chemical compounds from fructose and glucose from hydrolysates. The motivation is familiar from sustainable and economical kitchens: "nose-to-tail", i.e. utilizing all parts of a source. The research team is attempting something very similar with lignin production.

And they have succeeded in valorizing previously unused by-products of lignin production into a sought-after component of the plastics and food industry. "The complete utilization of the input materials and the high added value contribute enormously to increased economic efficiency in lignin production and make it a competitive, fossil-free alternative," according to the consensus of the researchers in the biorefinery groups from the three participating TU institutes. "From the small waste streams that remain, we produce energy or fertilizer for agriculture with the help of biogas plants."

A raw material with great potential

Due to its chemical nature, lignin can be used in a variety of ways, for example as a bio-based plastic or for the environmentally friendly production of medicines and flavorings. Experts therefore see the raw material as an opportunity to revolutionize the healthcare and energy industries, as well as the food supply. The challenge here is to keep the production of lignin economical and competitive with crude oil and other fossil fuels.

Read more

You can find more information on the website of the Institute of Thermal Process Engineering

Phosphorus can be removed from fodder plants with the aid of biocatalysis. This avoids nutrient-rich excretions from livestock that pollute soils and groundwater. And the scarce resource can be reused.

Phosphorus is an important building material for life. It is not only a component of bones, teeth and cells. The chemical element is involved in enabling humans and animals to produce and store energy. Feedstuffs such as cereal bran contain a lot of phosphorus in the form of phytic acid, but this is excreted undigested by animals with only one stomach, such as poultry and pigs. They lack certain digestive enzymes for this. As a result, a lot of phosphorus ends up on the fields as liquid manure, polluting the soil and groundwater. Research is now being carried out at the Technical University of Hamburg to find ways of reducing the phosphorus content of animal feed so that this environmentally harmful process is not set in motion in the first place.

Phosphorus is recycled

"We use rye bran for our research, which is a waste product from the flour industry anyway, but otherwise has excellent nutrient properties, explains Niklas Widderich, shaking a cylindrical glass vessel filled with light-colored bran powder. In a small fermenter, the process starts by adding water to the bran and creating a two-phase suspension. "Now the exciting part begins," says Widderich, who oversees the project at the Institute of Technical Biocatalysis. He uses biocatalysts in the form of enzymes. "The enzymes 'digest' the organically bound phosphorus, and the inorganic part, which we obtain from mineral sources, is retained. You can also say the phosphorus is predigested, because the resulting bran product can now be ingested by animals with single-part stomachs," the doctoral student explains. Thus, the animal is provided with a phosphorus supply that meets its needs, and excess phosphorus can be recycled and fed to other industries, such as the chemical and food industries. Next, the Hanover University of Veterinary Medicine comes into play as a project partner: "We have now produced enough feed in an extra-large fermenter so that the university can now test the digestibility of the feed in a six-week trial with animals," says process engineer Niklas Widderich.

Sustainable agriculture

In contrast to other methods in which phosphorus is only extracted at the end from already accumulated slurry (end-of-pipe approach), the TU project starts much earlier and regulates the phosphorus content in the feed already at the beginning of the value chain. Especially in the case of regionally concentrated animal husbandry, this type of feed can contribute to more sustainable agriculture because the soils are no longer oversupplied with phosphorus. Excess phosphorus leaches into groundwater and can promote algae growth in bodies of water. Legislators have therefore already increasingly reduced corresponding limits for the fertilization with phosphorus and thus the area-specific application rates to date.
Against the backdrop of steadily rising population figures - the eight billionth person was recently born - this TU project can take on even greater significance. As arable land is in short supply worldwide, fertilizer use is increasing. More phosphate rock must be mined for fertilizer production than can be regenerated over geologic time periods. Consequently, phosphorus sources are in danger of drying up. The European Union has already declared phosphate rock a non-renewable resource. Therefore, projects like Niklas Widderich's are particularly important for resource management in the context of a circular bioeconomy.

PhANG is the name of the project on phosphorus-adapted feedstuffs, which involves the Technical University of Hamburg, RWTH Aachen University and the University of Veterinary Medicine Hannover.

Scientists at the Institute of Technical Microbiology are examining the wastewater of breweries and municipalities for substances that can be used to produce electricity or hydrogen.

The project focuses its work on analyzing wastewater for organic substances that serve as substrates for microorganisms. Brewery wastewater, wastewater from the cellulose filter industry and municipal wastewater are particularly suitable for treatment. The substances multiply in so-called microbial fuel cells (MFC) or microbial electrolysis cells (MEC).

Setting the flow of electricity in motion

To understand this process, it is helpful to imagine a battery. In it, current is generated by the electrochemical flow of electrons from the anode to the cathode. Similarly, in the early 20th century, it was first observed that some species of bacteria were capable of transferring electrons to an anode, this was later called a "microbial fuel cell." Since then, many basic mechanisms of electron transfer have been studied, but a deeper understanding of the processes is needed to optimize and commercialize these processes.

Every day, large amounts of wastewater are generated from industry as well as from private households. Proper treatment and purification is mandatory before returning the water to the environment. However, this process consumes a lot of energy and/or chemicals. For this reason, great efforts are being made worldwide to develop novel methods for environmentally friendly, resource-saving wastewater treatment. "A pioneering biological process is the microbial fuel cell, as organic carbon can be removed from wastewater and electrical power can be generated at the same time" says project supervisor Ahmed Elreedy.

The concept of this process is based on the ability of some microorganisms to transfer electrons directly or indirectly to external insoluble electron acceptors such as electrodes. Electrons, protons and CO2 are produced during the biological oxidation of organic matter in the anode. This process is the basis for energy conservation and growth of microorganisms. To generate a flow of electrons (electric current), the oxygen present in the cathode is reduced by the excess electrons. What remains is water. For example, treating one cubic meter of domestic wastewater can generate electricity of up to 1000 amperes.

Wastewater becomes clean

The fundamentals of electron transfer to an anode have only been partially studied and remain the subject of current research. "Our work, in addition to studying these electron transfer processes, is mainly focused on evaluating and optimizing process efficiency when dealing with real industrial wastewater," explains Ahmed Elreedy. "With this technology, we are not only able to purify water in a resource-saving way, but at the same time use this wastewater as a substrate for the sustainable generation of electric power," he said.

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Ahmed Elreedy works as a research associate at the Institute of Technical Microbiology at Hamburg University of Technology. His research focuses on biological wastewater treatment with simultaneous energy generation using bioelectrochemical systems.