The unusual di‐domain structure of Dunaliella salina glycerol‐3‐phosphate dehydrogenase enables direct conversion of dihydroxyacetone phosphate to glycerol. (26th December 2019) - He, Qinghua
Summary: Dunaliella has been extensively studied due to its intriguing adaptation to high salinity. Its di‐domain glycerol‐3‐phosphate dehydrogenase (GPDH) isoform is likely to underlie the rapid production of the osmoprotectant glycerol. Here, we report the structure of the chimeric Dunaliella salina GPDH ( Ds GPDH) protein featuring a phosphoserine phosphatase‐like domain fused to the canonical glycerol‐3‐phosphate (G3P) dehydrogenase domain. Biochemical assays confirm that Ds GPDH can convert dihydroxyacetone phosphate (DHAP) directly to glycerol, whereas a separate phosphatase protein is required for this conversion process in most organisms. The structure of Ds GPDH in complex with its substrate DHAP and co‐factor nicotinamide adenine dinucleotide (NAD) allows the identification of the residues that form the active sites. Furthermore, the structure reveals an intriguing homotetramer form that likely contributes to the rapid biosynthesis of glycerol. Significance Statement: Green alga Dunaliella has a remarkable ability to thrive at high salinity environments. Structural and biochemical characterization of the glycerol‐3‐phosphatase fused glycerol‐3‐phosphate dehydrogenase protein boosts our understanding of the glycerol‐mediated salt‐resistance mechanism that can potentially benefit industrial and agricultural applications.