Enzymatic N-Acylation Step Enables the Biocatalytic Synthesis of Unnatural Sialosides

Reversible and chemoselective: Chitin is one of the most abundant and cheaply available biopolymers in Nature. Chitin has become a valuable starting material for many biotechnological products through manipulation of its N ‐acetyl functionality, which can be cleaved under mild conditions using the enzyme family of de‐ N ‐acetylases. However, the chemo‐selective enzymatic re‐acylation of glucosamine derivatives, which can introduce new stable functionalities into chitin derivatives, is much less explored. Here we describe an acylase (CmCDA from Cyclobacterium marinum ) that catalyzes the N ‐acylation of glycosamine with a range of carboxylic acids under physiological reaction conditions. This biocatalyst closes an important gap in allowing for the conversion of chitin to complex glycosides, such as C5‐modified sialosides, through the use of highly selective enzyme cascades.