Computational Characterisation of Sulphate-Reducing Bacteria Inhibitors to Overcome Methanogenic Competence and Optimise Green Biogas Production

Microorganisms such as methanogenic archaea play a key role in wastewater treatment plants (WWTPs) by breaking down organic matter and pollutants and producing methane, a potential renewable energy source. However, sulphate-reducing bacteria (SRB) compete with archaea for the same substrates under anaerobic conditions, lowering methane production and generating harmful hydrogen sulphide (H₂S). Inhibiting SRB is therefore crucial to enhance methane yield and reduce toxic by-products. By means of manual screening of public databases (KEGG, BRENDA, PDB, PubChem) 12 potential inhibitors of SRB were found. After computational ecotoxicological assessment, four candidates were selected, and one of them experimentally increased methane production, demonstrating that SRB inhibition favours the anaerobic digestion of sludges. In order to further explore new candidates, Quantitative Structure–Activity Relationship (QSAR) models were developed showing reliable predictive performance. These models enabled the virtual screening of COCONUT, a natural product database, identifying 73 potential SRB inhibitors. After an ecotoxicological assessment, five commercially available compounds remained. The identified candidates may reduce competition between SRB and methanogenic archaea, leading to higher methane production and supporting WWTPs in generating their own biogas. This would contribute to a circular economy and help mitigate greenhouse gas emissions.