An Enzymatic N‐Acylation Step Enables the Biocatalytic Synthesis of Unnatural Sialosides

• Published in: Angewandte Chemie International Edition 2020-03, Vol.59 (13), p.5308-5311
• Main Authors: Laborda, Pedro, Lyu, Yong‐Mei, Parmeggiani, Fabio, Lu, Ai‐Min, Wang, Wen‐Jiao, Huang, Ying‐Ying, Huang, Kun, Guo, Juan, Liu, Li, Flitsch, Sabine L., Voglmeir, Josef
• Format: Article
• Language: English
• Subjects: Acylation; Amides - chemistry; Amidohydrolases - metabolism; Biocatalysis; Biopolymers; Carboxylic acids; Carboxylic Acids - chemistry; Chitin; Chitin - chemistry; chitin de-N-acetylases; Derivatives; enzymatic synthesis; Enzymes; Glucosamine; Glucosamine - chemistry; Glycosides; Glycosides - chemical synthesis; glycosylation; Molecular Conformation; Stereoisomerism; Sugar Acids - chemical synthesis; Sugar Acids - chemistry; unnatural sialosides
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201914338

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 chemoselective enzymatic re‐acylation of glucosamine derivatives, which can introduce new stable functionalities into chitin derivatives, is much less explored. Herein 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 the conversion of chitin into complex glycosides, such as C5‐modified sialosides, through the use of highly selective enzyme cascades. Reversible and chemoselective: The enzyme Cyclobacterium marinum chitobiose deacetylase, which is highly selective for monomeric GlcNAc as a substrate, catalyzes the N‐acylation of glucosamine with carboxylic acids under physiological reaction conditions. This biocatalyst was applied in the first fully enzymatic synthesis of a series of C5‐modified sialosides starting from glucosamine and a series of non‐activated carboxylic acids.