Unidirectional mannitol synthesis ofAcinetobacter baumanniiMtlD is facilitated by the helix–loop–helix-mediated dimer formation

Abstract

SignificanceMannitol biosynthesis is essential forAcinetobacter baumanniito cope with osmotic stress. Currently, onlyPseudomonas putida,Acinetobacter baylyi, andA. baumanniiare able to de novo synthesize mannitol by a structurally unique bifunctional mannitol-1-phosphate dehydrogenase/phosphatase (AbMtlD). The molecular mechanism of reduction and dephosphorylation of fructose-6-phosphate to mannitol is highly dependent on the substrate shuffling from one protomer to the other protomer by a unique helix–loop–helix domain–mediated dimer formation, thus ensuring unidirectional and efficient biosynthesis of mannitol. These observations support an evolutionary adaptation of AbMtlD by fusion of dehydrogenase and phosphatase domains to facilitate efficient unidirectional enzymatic production of mannitol, unifying regulatory control and minimizing the intracellular concentration of toxic mannitol-1-phosphate during salt stress.