Strain software: a new tool will help to "program" the properties of bacteria

Scientists have developed a program that automatically analyzes the metabolic features of bacteria. The tool allows you to quickly determine which beneficial substances, such as vitamins, are capable of synthesizing microorganisms, which helps to assess the potential of certain species for biotechnology. The software is planned to be used in the search for strains that can be used as probiotics and other dietary supplements. It will also make it possible to produce fermented dairy products with specified beneficial properties, biotechnology experts told Izvestia.

Software for finding useful strains

Scientists from the Don State Technical University, I.M. Sechenov First Moscow State Medical University and Wageningen University (the Netherlands) have developed the KEGGaNOG tool, which will help specialists quickly assess the metabolic capabilities of bacteria. According to the researchers, microorganisms are widely used in biotechnology for the production of vitamins, antibiotics, enzymes valuable for medicine and chemistry, and many other substances. In addition, some of them are included in probiotic preparations that improve digestion and strengthen the immune system.

To understand how useful a particular type of bacteria is for humans, it is necessary to decode its genome, since the ability to synthesize useful compounds is determined by the presence of appropriate genes. However, the synthesis of most such substances, such as vitamins, involves several stages, so scientists first have to look for a number of different genes, determine the function for each of them, and then draw up a diagram of the metabolic pathways (chains of chemical transformations within the framework of metabolism) in which they are involved. When hundreds of bacterial species need to be analyzed, this process turns out to be extremely long and time-consuming.

"We started developing this tool when we encountered difficulties in quickly and reproducibly analyzing the intestinal microbial communities of bats. This is what prompted us to create a convenient method for analyzing bacterial genomes and metagenomes," Igor Popov, a researcher at Don State Technical University, told Izvestia.

KEGGaNOG acts as a link between two widely used programs by geneticists and biotechnologists — eggNOG-mapper and KEGG-Decoder. The first allows you to determine the functions of all the genes in any genetic sequence. The authors of the work have made it so that the data file from this program is automatically uploaded to a new one, which in turn extracts codes corresponding to certain genes or biochemical reactions from it. The developed software then transmits these codes to the KEGG Decoder, which calculates how fully the various metabolic pathways are represented in the genome.

The program visualizes the data obtained by creating heat maps, diagrams and graphs that clearly show which parts of the cellular metabolism of the organism under study are fully functional and which are absent.

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The researchers tested the tool on the genomes of 11 bacteria, including bifidobacteria and lactobacilli used as probiotics in dairy products. The instrument not only confirmed the already known metabolic features of these strains, but also showed the differences between them. This tool will allow you to quickly understand which strains are best suited for the production of certain vitamins and other beneficial compounds. In microbial ecology, the program will help to more accurately determine the role of microorganisms in the circulation of substances and interactions in ecosystems.

— The proposed tool makes it possible to turn genetic sequences into an informative picture of the metabolic potential of bacteria. Thanks to this, specialists, after performing only a few simple operations, will be able to get ready—made visualization and understand which strain produces the compound of interest more efficiently," Ilya Popov, a graduate student and junior researcher at Don State Technical University, told Izvestia.

Smart dairy products

The classical analysis of bacterial genomes, metagenomes, and their metabolic pathways is a very complex and time—consuming process. The developed tool can significantly reduce the volume and time, and most importantly, the cost of initial research, Vladimir Zhukov, founder of the Biotech club and expert at Boiling Points Omsk, NTI expert, director of the technology company BruttoNetto, told Izvestia.

— This tool can be used at the design stage of a functional food, medical or pharmaceutical product. Using the program, you can create a technological product, not copying, but overtaking competitors. But it is important to remember that this does not negate the need for standard microbiological and biochemical studies," the expert said.

The proposed tool is like a navigator in the world of bacteria, showing scientists where their hidden and not always obvious metabolic pathways lead, molecular biologist Arina Kholkina commented on the development. Now, instead of a long and confusing search, researchers can see in a couple of minutes what substances each bacterium is capable of producing — vitamins, amino acids, or other metabolites that affect the human body.

"This tool opens up new horizons not only for biotechnology, medicine and pharmaceuticals, but also for the food industry: producers of probiotics and live yoghurts can finally understand exactly which strains really work and which do not bring results," said the expert.

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The development provides an opportunity to move from general ideas about the benefits of probiotics to precise, measurable parameters, said Konstantin Derevskov, founder of the Q-CHECK digital platform and food safety expert.

"There is great potential here to create the next generation of functional food products, where we are gradually abandoning universal solutions, and now, using the example of kefir, we can talk not just about fermenting milk, but about purposefully designing its beneficial properties," he said.

For example, based on a new technology, you can create a line of fermented products for a specific task. One product, using selected strains, will be aimed at supporting the natural production of B vitamins, and the other, for example, at synthesizing substances to strengthen bone tissue. In fact, we are getting our hands on a scientifically based designer for creating personalized nutrition, the expert noted.

— Scientists use the bacterial community not only in the food industry, but also in the pharmaceutical industry, including microbacteria. If we understand what kind of array of genes we see, it can greatly accelerate the entire field of industrial microbiology," said Mikhail Charny, a leading expert at the FoodNet NTI working group.

The results of the study, supported by a grant from the Russian Science Foundation (RSF), are published in the journal Molecular Nutrition & Food Research.