Toward universal donor blood: Enzymatic conversion of A and B to O type

Abstract

Transfusion of blood, or more commonly red blood cells (RBCs), is integral to health care systems worldwide but requires careful matching of blood types to avoid serious adverse consequences. Of the four main blood types, A, B, AB, and O, only O can be given to any patient. 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. 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. Thus, conversion of A, B, and AB RBCs to O-type RBCs should be achievable by removal of that sugar with an appropriate glycosidase. 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. 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. 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. This promising system works well both in standard conditions and in whole blood. We discuss remaining challenges and opportunities for the use of such enzymes in blood conversion and organ transplantation.

Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort

“…A variety of bacteria metabolize blood antigens, with potential applications in synthetic universal donor blood production 42,43 . Gut bacteria are particularly exposed to A- and B- antigens in the gut mucosa of secretor individuals 44 .…”

Protein Glycoengineering: An Approach for Improving Protein Properties

“…In recent years, the application of glycosidases and glycosyltransferases to protein glycoengineering, including the development of a cell-free glycoprotein synthesis technology, has greatly advanced this field (Jaroentomeechai et al, 2018 ; Wen et al, 2018 ; Kightlinger et al, 2019 ; Moremen and Haltiwanger, 2019 ; Rahfeld and Withers, 2020 ). A prominent aspect in the advance is to make us realize the importance of subtle variations in glycan structures to protein performance (Washburn et al, 2015 ).…”

“…in excellent review articles by Saxon and Bertozzi (2001), Sola et al (2007), Gamblin et al (2009), Wolfert and Boons (2013), Krasnova and Wong (2016), Wu et al (2017), Sun et al (2018), Wen et al (2018), Guberman and Seeberger (2019), Moremen and Haltiwanger (2019), and Rahfeld and Withers (2020).…”

“…Detailed discussions of these efforts are beyond the scope of this review. The necessary information about these research studies can be found in excellent review articles by Saxon and Bertozzi ( 2001 ), Sola et al ( 2007 ), Gamblin et al ( 2009 ), Wolfert and Boons ( 2013 ), Krasnova and Wong ( 2016 ), Wu et al ( 2017 ), Sun et al ( 2018 ), Wen et al ( 2018 ), Guberman and Seeberger ( 2019 ), Moremen and Haltiwanger ( 2019 ), and Rahfeld and Withers ( 2020 ).…”

Characteristics and expression patterns of six α-galactosidases in cucumber (Cucumis sativus L.)

“…In this study, full-length cDNA of six putative α-Gal genes were in vitro expressed and characterized, and their expression pattern during leave development and seed germination were investigated. Furthermore, α-Gals are widely used in food and feed industry to eliminate anti-nutritional factors and in medicinal field for treatment of Fabry disease or blood enzymatic conversion of A and B to O type [ 27 , 28 ]. Therefore, the illumination of enzyme properties of cucumber α-Gals was also beneficial for accelerating industrial application of plant originated α-Gals.…”