Kifunensine

Kifunensine is an alkaloid originally isolated from Kitasatosporia kifunense, an actinobacterium (formerly called an actinomycete). It is a neutral, stable compound. Kifunensine is an alkaloid originally isolated from Kitasatosporia kifunense, an actinobacterium (formerly called an actinomycete). It is a neutral, stable compound. Kifunensine is a potent inhibitor of the mannosidase I enzyme and is primarily used in cell culture to make high mannose glycoproteins. Inside a cell, it prevents endoplasmic reticulum mannosidase I (ERM1) from trimming mannose residues from precursor glycoproteins. Kifunensine shows no inhibitory action against mannosidase II or the endoplasmic reticulum alpha-mannosidase, and it weakly inhibits arylmannosidase. When incorporated in cell culture media, kifunensine has shown no significant impact on cell growth or glycoprotein production yield. Kifunensine has shown potential for treatment of sarcoglycanopathies and lysosomal storage disorders. Kifunensine was first isolated by Iwami et al. in 1987, and described as a new type of immunoactive substance. It was originally prepared by culturing the actinobacterium Kitasatosporia kifunense in a suitable medium at 25–33 °C for several days, followed by extraction of the alkaloid. The structure of kifunensine was published in 1989 by Kayakiri et al. Kifunensine is a potent inhibitor of the mannosidase I enzyme. It is 50 to 100 times more potent than deoxymannojirimycin – an alkaloid with a similar structure. Kifunensine inhibits human endoplasmic reticulum α-1,2-mannosidase I and Golgi Class I mannosidases IA, IB and IC with Ki values of 130 and 23 nM, respectively.