Breakthrough in tracking biocatalysis by single cells opens up new possibilities in "green chemistry"
The transformation of chemical compounds by living cells - so-called whole-cell biocatalysts - is a process that has been known for some time and has led to a wealth of interesting products. This is evident, for example, in traditional processes such as bread baking or beer brewing, where molecules produced by yeast fungi contribute significantly to flavor. Highly complex chemical molecules such as vitamins or pharmaceuticals can also be produced using this principle. Similar to beer brewing, this happens under very resource-efficient conditions: The reaction is carried out in large vessels (fermenters) in which the starting compounds are converted into valuable products in an aqueous nutrient medium by millions of living cells that serve as biocatalysts. Researchers at the University of Leipzig have now succeeded in shrinking the fermenter vessels in such a way that, for the first time, the biocatalysis of individual cells can be studied.
A key to the breakthrough was the use of microfluidic technology, in which liquid flows in hair-thin channels of microchips can be controlled in a targeted manner. This enabled the production of nanoliter-tiny droplets in which individual yeast cells were placed. Advanced analytical techniques were used to chemically analyze the droplet contents to precisely quantify the products generated in the nanoliter vessels. How this was achieved is described by the team led by Detlev Belder from the Institute of Analytical Chemistry at the University of Leipzig in an article now published in the renowned journal "Angewandte Chemie".
,,It has been known for some time that living cells show the most heterogeneous characteristics, for example in terms of their growth or metabolism. There is evidence that the millions of cells in fermenters behave in a similar way to working communities of other species, for example, that 30 percent of the individuals do 90 percent of the effective work, for example in the manufacture of products," explains Belder. In biocatalysis, researchers have so far literally been groping in the dark because the substances produced are usually invisible under the microscope. But here, too, it could be that a cell is very productive in the synthesis of a drug, for example, while its neighbors are barely active or doing the wrong thing.
Since the researchers at the University of Leipzig were able to shrink the fermenter vessels so that the biocatalysis of individual cells can be studied for the first time, this opens up completely new possibilities in "green chemistry": Highly productive cells from the cell colony could now be identified and the most efficient strains could be bred to achieve higher yields, for example for expensive fine chemicals," says the chemist. In addition, it would be possible to study individual cells in detail with regard to the reaction mechanism, metabolism or catalytic efficiency.
The reaction-accelerating properties of biocatalysts represent a central building block for sustainable "green chemistry". Unlike in classical chemical synthesis, no organic solvents, toxic additives or harsh reaction conditions are required.
Title of original publication in the journal Angewandte Chemie:
,,Quantification of Biocatalytic Transformations by Single Microbial Cells Enabled by Tailored Integration of Droplet Microfluidics and Mass Spectrometry" , doi.org/10.1002/anie.202204098