100% IdoA; thus, the name CS/DS is assigned to describe the hybrid nature of the chain. DS-epi1 and DS-epi2, which are encoded by Dse and Dse-like (Dsel), respectively, mediate the epimerization of a carboxyl group at C5 to form IdoA in CS/DS (Maccarana et al., 2006; Pacheco et al., 2009b). Dse-knockout mice have connective tissue fragility attributed to a CS/DS alteration of decorin, which results in impaired assembly of collagen fibrils (Maccarana et al., 2009; Gustafsson et al., 2014), and a series of malformations whose cause is not understood. In contrast, the loss of Dsel results in normal offspring (Bartolini et al., 2012). Double-knockout mice die around birth and completely lack IdoA in their CS/DS chains, which indicates that DS-epi1 and DS-epi2 are the only epimerases in DS biosynthesis (Stachtea et al., 2015). DS-epi1, which was originally referred to as squamous cell carcinoma antigen recognized by cytotoxic T lymphocytes 2 (SART2) (Nakao et al., 2000; Maccarana et al., 2006), is overexpressed in all tumors and functionally linked to the tumorigenic properties of esophagus squamous cell carcinoma that involve cell migration (Thelin et al., 2012). Nevertheless, it is not clear how a modified CS/DS chain leads to developmental abnormalities and malignancy.
