The Mesomeric Effect of Thiazolium on non‐Kekulé Diradicals in Pichia stipitis Transketolase

It is theoretically plausible that thiazolium mesomerizes to congeners other than carbene in a low effective dielectric binding site; especially given the energetics and uneven electronegativity of carbene groups. However, such a phenomenon has never been reported. Nine crystal structures of transketolase obtained from Pichia stipitis (TKps) are reported with subatomic resolution, where thiazolium displays an extraordinary ring‐bending effect. The bent thiazolium congeners correlate with non‐Kekulé diradicals because there is no gain or loss of electrons. In conjunction with biophysical and biochemical analyses, it is concluded that ring bending is a result of tautomerization of thiazolium with its non‐ Kekulé diradicals, exclusively in the binding site of TKps. The chemophysical properties of these thiazolium mesomers may account for the great variety of reactivities carried out by thiamine–diphosphate‐containing (ThDP) enzymes. The stability of ThDP in living systems can be regulated by the levels of substrates, and hydration and dehydration, as well as diradical‐mediated oxidative degradation. Die Aromatizität von Thiazolium wird als essenziell für die katalytische Effizienz von Thiamindiphosphat enthaltenden Enzymen angesehen. Eine Verkrümmung des Thiazoliums wurde als Ursache für die große Vielfalt von Reaktivitäten dieser Enzyme identifiziert.