Biocatalytic Transfer of Pseudaminic Acid (Pse5Ac7Ac) Using Promiscuous Sialyltransferases in a Chemoenzymatic Approach to Pse5Ac7Ac-Containing Glycosides

Pseudaminic acid (Pse5Ac7Ac) is a nonmammalian sugar present on the cell surface of a number of bacteria including Pseudomonas aeruginosa, Campylobacter jejuni, and Acinetobacter baumannii. However, the role Pse5Ac7Ac plays in host–pathogen interactions remains underexplored, particularly compared to its ubiquitous sialic acid analogue Neu5Ac. This is primarily due to a lack of access to difficult to prepare Pse5Ac7Ac glycosides. Herein, we describe the in vitro biocatalytic transfer of an activated Pse5Ac7Ac donor onto glycosyl acceptors, enabling the enzymatic synthesis of Pse5Ac7Ac-containing glycosides. In a chemoenzymatic approach, chemical synthesis initially afforded access to a late-stage Pse5Ac7Ac biosynthetic intermediate, which was subsequently converted to the desired CMP-glycosyl donor in a one-pot two-enzyme process using biosynthetic enzymes. Finally, screening a library of 13 sialyltransferases (SiaT) with the unnatural substrate enabled the identification of a promiscuous inverting SiaT capable of turnover to afford β-Pse5Ac7Ac-terminated glycosides.</p

Clinical bioethics integration, sustainability, and accountability: the Hub and Spokes Strategy

The "lone" clinical bioethicist working in a large, multisite hospital faces considerable challenges. While attempting to build ethics capacity and sustain a demanding range of responsibilities, he or she must also achieve an acceptable level of integration, sustainability, and accountability within a complex organisational structure. In an effort to address such inherent demands and to create a platform towards better evaluation and effectiveness, the Clinical Ethics Group at the Joint Centre for Bioethics at the University of Toronto is implementing the Hub and Spokes Strategy at seven hospitals. The goal of the Hub and Spokes Strategy is to foster an ethical climate and strengthen ethics capacity broadly throughout healthcare settings as well as create models in clinical bioethics that are excellent and effective