Two radical-dependent mechanisms for anaerobic degradation of the globally abundant organosulfur compound dihydroxypropanesulfonate

Abstract

<jats:p>2(<jats:italic>S</jats:italic>)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 10<jats:sup>10</jats:sup>tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling by microbes, thus, play important roles in the biogeochemical sulfur cycle. However, DHPS degradative pathways in the anaerobic biosphere are not well understood. Here, we report the discovery and characterization of two O<jats:sub>2</jats:sub>-sensitive glycyl radical enzymes that use distinct mechanisms for DHPS degradation. DHPS-sulfolyase (HpsG) in sulfate- and sulfite-reducing bacteria catalyzes C–S cleavage to release sulfite for use as a terminal electron acceptor in respiration, producing H<jats:sub>2</jats:sub>S. DHPS-dehydratase (HpfG), in fermenting bacteria, catalyzes C–O cleavage to generate 3-sulfopropionaldehyde, subsequently reduced by the NADH-dependent sulfopropionaldehyde reductase (HpfD). Both enzymes are present in bacteria from diverse environments including human gut, suggesting the contribution of enzymatic radical chemistry to sulfur flux in various anaerobic niches.</jats:p>

Sulfoquinovose is a select nutrient of prominent bacteria and a source of hydrogen sulfide in the human gut

“…Highly oxygen-sensitive glycyl radical enzymes are a diverse and abundant protein family of the human gut microbiota, yet largely remain functionally uncharacterized [ 63 ]. In accordance with findings by Liu et al [ 18 ], DHPS was desulfonated into sulfite and hydroxyacetone by HpsGH (Fig. S5E ) in cell-free extracts of DHPS-grown B. wadsworthia cells, but only when assayed under strictly anoxic conditions (Fig.…”

“…2C, D , Fig. S5C–E ) that was recently identified and characterized [ 18 ]. HpsG is a closely related but phylogenetically distinct paralog of isethionate (2-sulfoethanol) sulfite-lyase IslA [ 28 ] (also designated IseG [ 62 ]) (60.6% identity to HpsG) in B. wadsworthia (Fig.…”

“…IslA catalyzes isethionate desulfonation, a key reaction in taurine degradation [ 28 , 62 ]. HpsH is the activator of HpsG [ 18 ], analogous to the IslA-activating, radical SAM enzyme IslB [ 28 ]. Accordingly, hpsG and hpsH were the most differentially expressed B. wadsworthia genes in the SQ-degrading fecal microcosms (n-fold change of 83 and 93, respectively; P = 3.8 × 10 −8 and 1.0 × 10 −5 , respectively, Fig.…”

“…The intestinal strains of the Firmicutes species Enterococcus gilvus , Clostridium symbiosum , and Eubacterium rectale also expressed SFT pathway genes during anaerobic, fermentative growth with SQ [ 15 ]. Bacterial SQ-degradation products are the excreted C 3 -organosulfonates 2,3-dihydroxypropane-1-sulfonate (DHPS) or 3-sulfolactate, which can serve as sources of sulfite via diverse catabolic pathways of specialized sulfite-respiring and H 2 S-producing Desulfovibrionaceae species [ 17 , 18 ]. Although mammalian cells also produce H 2 S in the cytoplasm and in mitochondria [ 19 ], bacteria that anaerobically respire sulfite derived from sulfate or taurine are considered the main sources of H 2 S in the intestine [ 20 , 21 ].…”

Protein Dynamics and Substrate Protonation State Mediate the Catalytic Action of Trans-4-Hydroxy-L-Proline Dehydratase

“…15 HypD is one of the most abundant glycyl radical enzymes (GREs) in the healthy human gut microbiome 15 and is considered a promising antibiotic target for the prominent antibiotic-resistant pathogen Clostridium difficile. [15][16][17][18] Along with glycerol dehydratase (GD), propanediol dehydratase (PD), choline trimethylamine-lyase (CutC), isethionate sulfite-lyase (IslA), 2(S)dihydroxypropanesulfonate-sulfolyase/dehydratase (HpsG/HpfG), 19 HypD belongs to the 1,2eliminase class of GREs, which are essential for anaerobic primary and secondary metabolism in bacteria and archaea. 16,[20][21][22][23] Common to all members of the GRE superfamily, HypD involves an evolutionarily conserved glycine-centered radical in the active site, which is installed by a cognate S-adenosylmethionine (AdoMet)-dependent activating enzyme.…”