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Human chitinolytic enzymes trigger growing interest, not only because a wide range of diseases and allergic responses are linked to chitinous components of pathogens, including their interplay with human enzymes, but also due to the increasing use of chitosans in biomedical applications. Here, we present a detailed side-by-side analysis of the only two human chitinases, chitotriosidase and acidic mammalian chitinase, as well as human lysozyme. By analyzing the cleavage of well-characterized chitosan polymers and defined chitin and chitosan oligomers, we report mild processivity and a quantitative subsite preference typical for GH18 chitinases for chitotriosidase and acidic mammalian chitinase. In contrast, lysozyme is negligibly processive and preferentially binds acetylated units at subsites -2, -1, and +1, thus exhibiting an even higher overall preference for acetylated units. A common feature of all three enzymes is their endo-chitinase behavior. For efficient hydrolysis, chitotriosidase or lysozyme require substrates of ≥4 or ≥5 units, respectively, and we identified defined chitosan oligomers which can competitively inhibit chitotriosidase. Knowledge about the enzymes' actions provides insight into the metabolic fate of chitin and chitosans in the human body, which is crucial to develop and approve chitosan applications, and to elucidate molecular mechanisms in chitin-associated diseases.
Hellmann et al. (Sat,) studied this question.