Novel insights into the existence of the putative UDP-glucuronate 5-epimerase specificity

C5-epimerases are promising tools for the production of rare l-hexoses from their more common d-counterparts. On that account, UDP-glucuronate 5-epimerase (UGA5E) attracts attention as this enzyme could prove to be useful for the synthesis of UDP-l-iduronate. Interestingly, l-iduronate is known as a precursor for the production of heparin, an effective anticoagulant. To date, the UGA5E specificity has only been detected in rabbit skin extract, and the respective enzyme has not been characterized in detail or even identified at the molecular level. Accordingly, the current work aimed to shed more light on the properties of UGA5E. Therefore, the pool of putative UGA5Es present in the UniProt database was scrutinized and their sequences were clustered in a phylogenetic tree. However, the examination of two of these enzymes revealed that they actually epimerize UDP-glucuronate at the 4- rather than 5-position. Furthermore, in silico analysis indicated that this should be the case for all sequences that are currently annotated as UGA5E and, hence, that such activity has not yet been discovered in nature. The detected l-iduronate synthesis in rabbit skin extract can probably be assigned to the enzyme chondroitin-glucuronate C5-epimerase, which catalyzes the conversion of d-glucuronate to l-iduronate on a polysaccharide level.

Jaar van publicatie:2020

Toegankelijkheid:Open