Mirror substrates specificity of a 2, 3-dihydroxypropanesulfonate degrading enzyme in sulfate-reducing bacteria

Ubiquitous R- and S-enantiomers of 2,3-dihydroxypropanesulfonate (DHPS), organic sulfur compounds produced by photosynthetic organisms, serve as common nutrient and energy sources for specific bacteria. While most known DHPS-degrading enzymes exhibit enantioselectivity, this study introduces a unique dehydrogenase, DhpA from the sulfate-reducing bacterium Desulfovibrio sp. DF1, capable of efficiently metabolizing both R- and S-DHPS to 3-sulfolactaldehyde (SLA). The crystal structure of DhpA reveals a conserved binding pocket that recognizes the sulfonate group of DHPS through interactions with Lys123, Ser174, and Asn175. The catalytic mechanism of the enzyme involves the oxidation of the C3-OH group of both enantiomers, facilitated by the Lys171. The mutation of Lys171 significantly diminishes activity, confirming its critical role in catalysis. Based on biochemical and genetic analyses, this study proposes a chiral DHPS degradation pathway in bacteria. This study reveals the unique enantiomeric selectivity of DhpA, expanding our understanding of the bacterial metabolism of chiral molecules.