Reductive-Oxidative Biodegradation of Bisphenol A under the Nitrate-Reducing Conditions: The Interplay with Carbon Metabolism and Nitrate Assimilation

Bisphenol
A (BPA), a representative endocrine-disrupting
chemical,
poses significant threats to human and ecological health. While microbial
BPA degradation under aerobic conditions is well-documented, the initiation
and performance of degradation by alternative electron acceptors remain
poorly characterized. In this study, we identified a reductive-oxidative
pathway in an isolated Klebsiella pneumoniae strain under nitrate-reducing conditions. BPA degradation reached
49.7% within 120 h with NO3––N
(10 mg/L) and glucose (7.5 g/L). Untargeted metabolomics proposed
a sequential reductive-oxidative pathway: BPA was first reduced to
2,2-diphenylpropane (DPP), then hydroxylated, and cleaved by hydroxylases
and dioxygenases (e.g., BsdC, HcaB). Isothermal titration calorimetry
and molecular dynamics confirmed the key roles of the enzyme in BPA
biodegradability, and proteomics revealed that metabolic reprogramming
drove BPA degradation under nitrate-reducing conditions. Specifically,
BPA upregulated carbon-metabolism enzymes to generate reducing equivalents
for the initial reduction. Subsequent electron transfer from oxidized
DPP intermediates, coupled with an assimilatory nitrate reduction,
enabled complete degradation. These findings provide novel mechanistic
insights into BPA biodegradation under nitrate-reducing conditions
and establish a theoretical basis for bioremediation strategies in
contaminated anaerobic ecosystems.