An Aspergillus niger strain developed by BRAIN Biotech has proven to be a high-performance production strain for enzymes and alternative proteins – with yields in the double-digit gram-per-litre range. Interdisciplinary teamwork was the basis for this success.
For the production of enzymes and proteins by microbial fermentation, BRAIN Biotech's project teams focus on interdisciplinarity: experts from microbiology, molecular biology and bioprocess development work in parallel on strain and bioprocess optimization. An Aspergillus niger strain developed by BRAIN Biotech has proven its suitability as an efficient production strain for enzymes and alternative proteins, with yields in the "double-digit" gram-per-liter range.
Case Study: A customer is looking for a microbial strain that produces a specific molecule in the highest possible quantity. How is such a production strain selected? Christian Naumer, Director & Unit Head Bioprocess Development at BRAIN Biotech, explains: "If the customer does not specify a strain, the team decides which microorganism to use after a scientific assessment of the target molecule. Usually, this is a strain that is already recognized as a production strain for the respective application and is classified as safe."
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In the future, a large proportion of animal proteins will be replaced by sequence-identical but microbially produced proteins.
- VP, Head of Research & Development BRAIN Biotech Zwingenberg
Production strains include Escherichia coli, Pichia pastoris (Komagataella phaffii), Bacillus subtilis and the filamentous fungus Aspergillus niger. The latter is particularly popular in biotechnology because it naturally secretes proteins in high titers and this property can be exploited.
The Aspergillus niger used at BRAIN Biotech belongs to biosafety level 1 (BSL1) and has already shown its potential in Zwingenberg several times. In Aspergillus niger, production successes with yields in the “double-digit” gram per liter range, which is relevant for industry, have long been demonstrated by the project teams for the secretion of homologous proteins. These yields are now also being achieved with heterologous proteins from eukaryotic hosts.
Alexander Pelzer, Head of Research and Development at BRAIN Biotech's R&D site in Zwingenberg, explains: "Aspergillus niger has played an important role in the production of enzymes for many years. Now, there are also many requests from the field of alternative proteins: in the future, animal proteins will be replaced by sequence-identical but microbially produced proteins.”
The economic production of microbially produced animal proteins for the food industry requires powerful microorganisms. To enable a microorganism to produce a target protein in high quantities, researchers often modify its metabolism. The molecular biologists at BRAIN Biotech achieve this "genetic engineering" with the help of genome editing and a very special enzyme: the nuclease G-dase M, an in-house development of BRAIN Biotech's Akribion Genomics team. Genome editing involves the targeted integration of multiple optimized gene expression cassettes encoding the target protein into the genome of the microorganism.
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We would not have recognized the potential of some microorganisms if we had not developed the respective process in parallel. This is especially true for bioprocesses with the complex organism Aspergillus niger.
- Director, Unit Head Bioprocess Development
In addition, the production organism is modified so that it ultimately produces only minimal amounts of unwanted proteins without reducing the secretion capacity for the target protein. The targeted deletion of the host's genes plays a crucial role in this process. The fewer "secondary proteins" the microorganism produces and secretes, the less complex the subsequent downstream process (DSP). Alexander Pelzer emphasizes: "Such a result is extremely important for our customers because it means a faster and more cost-effective production process - and ultimately a cheaper product.”
At BRAIN Biotech, strain optimization and bioprocess development are considered from the outset in an interdisciplinary task from the perspective of microbiology, molecular biology and bioprocess development. Alexander Pelzer formulates the idea as follows: "I need to improve the strain at the molecular level, but I also need to understand the strain in the bioreactor."
During the development of the production strain, the strain and the bioprocess are optimized in parallel. Christian Naumer can also confirm that the close teamwork at BRAIN Biotech has paid off: "We would not have recognized the potential of some microorganisms if we had not developed the respective process in parallel. This is especially true for bioprocesses with the complex organism Aspergillus niger.”
Keywords: Bioprocess development, alternative proteins, precision fermentation, production strains, genome editing, Aspergillus niger, DSP
→ Based on the developments and experience gained in recent years, we offer an Aspergillus platform for the production of a wide range of target proteins. Molecular and microbiological methods as well as bioprocess development are applied for the development of target-specific strains. The fermenters used in the first development phase have a volume of one to two liters. The interdisciplinary experience gained in the first phase will also benefit the next phase, the transfer of the process to a larger scale.
Do you have an enzyme or protein in mind and are looking for a production strain? We will find the right production organism, develop it specifically and set up the appropriate fermentation process.
Contact our BioScience team at BRAIN Biotech Zwingenberg
Website BRAIN Biotech Zwingenberg
