The study of the influence of various effectors is one of the priority areas of modern research in biochemistry, biocoordination chemistry, and biotechnology. One way to increase their activity is using various effector compounds capable of modifying the enzyme activity. Earlier, as a result of screening microorganisms of different taxonomic groups, we has selected active α-L-rhamnosidase and α-galactosidase producers. It is widely used in the food industry to improve the quality of soy products by hydrolyzing indigestible galactosides such as raffinose and stachyose, in the processing of raw materials in order to increase the yield of sugar from molasses, and for the biotransformation of human blood erythrocytes of group B (III) in universal donor erythrocytes, as well as in enzyme therapy of some congenital disorders of sphingolipid metabolism. α-Galactosidase finds application in many areas. These enzymes may enhance wine aroma and flavonoid bioavailability, or assist in the synthesis of pharmaceuticals. α-L-rhamnosidases may be applied for debittering of citrus fruit juices, due to the less bitter taste of the derhamnosylated flavonones, for rhamnose production, and for the determination of the anomeric configuration in polysaccharides, glycosides and glycolipids. These enzymes are considered useful for various applications. In recent years, the particular interest of researchers is focused on such enzymes as α-L-rhamnosidase and α-galactosidase. CRISPR/Cas9 mediated ABO geneedition allows the conversion of blood type A to universal type O in Rhnull donor‐derived hiPSCs A targeted knock‐in strategyallows to reproduce the c.261delG polymorphism present in the most commoninactive ABO*O.01 allele This work provides a newapproach potentially applicable to cell lines established from rare blood donorsnot carrying blood type O This work provides a paradigmatic example of an approach potentially applicable to other hiPSC lines derived from rare blood donors not carrying blood type O. Here, we present a CRISPR/Cas9‐mediated ABO gene edition strategy for the conversion of blood type A to universal type O, which we have applied to an Rhnull donor‐derived hiPSC line, originally carrying blood group A. In both scenarios, the potential use of human‐induced pluripotent stem cell (hiPSC)‐derived Rhnull red cells is also dependent on ABO compatibility. Rhnull red cells are critical for the transfusion of immunized patients carrying the same phenotype, besides its utility in the diagnosis of Rh alloimmunization when a high‐prevalence Rh specificity is suspected in a patient or a pregnant woman. One such phenotype is the Rhnull, which lacks all the Rh antigens on the red cell membrane and represents one of the rarest blood types in the world with only a few active blood donors available worldwide. The limited availability of red cells with extremely rare blood group phenotypes is one of the global challenges in transfusion medicine that has prompted the search for alternative self‐renewable pluripotent cell sources for the in vitro generation of red cells with rare blood group types. We discuss remaining challenges and opportunities for use of such enzymes in blood conversion and organ transplantation. This promising system works well both in standard conditions and in whole blood. In 2019, screening of a metagenomic library derived from the feces of an AB donor enabled discovery of a significantly more efficient two-enzyme system, involving a GalNAc deacetylase and a galactosaminidase, for A conversion. New α-galactosidases and α-N-acetylgalactosaminidases were identified by screening bacterial libraries in 2007, allowing improved conversion of B and the first useful conversions of A-type RBCs, although under constrained conditions. The first demonstration of a B-to-O conversion by Goldstein in 1982 required massive amounts of enzyme, but enabled proof-of-principle transfusions without adverse effects in humans. Thus, conversion of A, B, and AB RBCs to O-type RBCs should be achievable by removal of that sugar with an appropriate glycosidase. A and B blood differ from the O type in the presence of an additional sugar antigen (GalNAc and Gal, respectively) on the core H antigen found on O-type RBCs. This universal donor O-type blood is crucial for emergency situations where time or resources for typing are limited, so it is often in short supply. Of the four main blood types, A, B, AB, and O, only O can be given to any patient. Transfusion of blood, or more commonly red blood cells (RBCs), is integral to healthcare systems worldwide, but requires careful matching of blood types to avoid serious adverse consequences.
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