Comparative metabolic modeling of multiple sulfate‐reducing prokaryotes reveals versatile energy conservation mechanisms

Abstract

Sulfate-reducing prokaryotes (SRPs) are crucial participants in the cycling of sulfur, carbon, and various metals in the natural environment and in engineered systems.Despite recent advances in genetics and molecular biology bringing a huge amount of information about the energy metabolism of SRPs, little effort has been made to link this important information with their biotechnological studies. This study aims to construct multiple metabolic models of SRPs that systematically compile genomic, genetic, biochemical, and molecular information about SRPs to study their energy metabolism. Pan-genome analysis was conducted to compare the genomes of SRPs, from which a list of orthologous genes related to central and energy metabolism was obtained. Twenty-four SRP metabolic models via the inference of pan-genome analysis were efficiently constructed. The metabolic model of the well-studied model SRP Desulfovibrio vulgaris Hildenborough (DvH) was validated via flux balance analysis (FBA). The DvH model predictions matched reported experimental growth and energy yields, which demonstrated that the core metabolic model worked successfully.Further, steady-state simulation of SRP metabolic models under different growth conditions showed how the use of different electron transfer pathways leads to energy generation. Three energy conservation mechanisms were identified, including menaquinone-based redox loop, hydrogen cycling, and proton pumping. Flavin-based electron bifurcation (FBEB) was also demonstrated to be an essential mechanism for supporting energy conservation. The developed models can be easily extended to other species of SRPs not examined in this study. More importantly, the present work develops an accurate and efficient approach for constructing metabolic models of multiple organisms, which can be applied to other critical microbes in environmental and industrial systems, thereby enabling the quantitative prediction of their metabolic behaviors to benefit relevant applications.

Combining metabolic flux analysis with proteomics to shed light on the metabolic flexibility: the case of Desulfovibrio vulgaris Hildenborough

“…In both hydrogen-and formate-cycling model, electrons released in the periplasm are cycling back to the cytoplasm through transmembrane electron transport complexes, thus providing electrons for sulfate reduction and energy conservation in DvH (Keller and Wall, 2011;Tang et al, 2021). Among them, the quinone reductase complex (QrcDCBA) (Venceslau et al, 2010) and the transmembrane complex (TmcABCD) were identified with high confidence (Table 1) in these samples.…”

Microbial lactate utilisation and the stability of the gut microbiome

“…Lactate utilisation (Figure 1B) is carried out under microaerophilic conditions by Proteobacteria, including pathogens such as Campylobacter and Salmonella species, which fully oxidise lactate to carbon dioxide and water (Gillis et al, 2019). Desulfovibrio species, on the other hand, can convert lactate to acetate, together with the dissimilatory reduction of sulphate to sulphide (Marquet et al, 2009;Tang et al, 2021). Within the Firmicutes phylum, certain microbes are able to convert lactate to propionate or butyrate (Louis and Flint, 2017; Table 1).…”

“…Certain anaerobes have electron transport systems that work with alternative final electron acceptors. Thus, sulphate-reducing bacteria utilise sulphate to generate sulphide (Tang et al, 2021), and propionateproducing bacteria following the succinate pathway link the step from fumarate to succinate to electron transport (Seeliger et al, 2002).…”

“…Furthermore, lactate conversion to pyruvate is carried out by different enzymes and redox co-factors in different bacteria, for example, a lactate dehydrogenase involving a membrane-bound menaquinone is employed by Desulfovibrio spp. (Tang et al, 2021).…”

“…• Neurotoxicity of D-lactate Chan et al, 1994 • Destabilising impact on the gut microbiota through low pKa and differential growth inhibition; can lead to lactic acidosis, which is potentially fatal Duncan et al, 2009;Nocek, 1997;Wang et al, 2020 • Growth substrate for some pathogenic bacteria, e.g. Salmonella, C. jejuni Gillis et al, 2019;Thomas et al, 2011 • Co-substrate for sulphate-reducing bacteria, resulting in enhanced production of genotoxic H 2 S Marquet et al, 2009;Tang et al, 2021 • Possible promotion of virulence in some pathogens (e.g. C. albicans) Ballou et al, 2016;Llibre et al, 2021 butyrate, compared to patients with mild or quiescent disease.…”