Cr(VI) stress induces carbon-nitrogen metabolic reprogramming in Penicillium oxalicum SL2

Hexavalent chromium [Cr(VI)] detoxification by fungi is environmentally important, yet the metabolic basis that sustains extracellular non-enzymatic Cr(VI) reduction remains elusive. This study investigated extracellular Cr(VI) reduction and metabolic reprogramming in the Cr(VI)-tolerant filamentous fungus Penicillium oxalicum SL2. P. oxalicum SL2 efficiently reduced Cr(VI), with reduction efficiencies of 99.50 ± 0.57%, 38.54 ± 0.76%, and 29.84 ± 3.41% after 48 h at 100, 200, and 400 mg/L Cr(VI), respectively. At 100 mg/L Cr(VI), reduction was primarily mediated through an extracellular non‑enzymatic pathway, with cell‑free supernatant contributing over 90.0% of the total reduction activity. Metabolomics showed a concentration‑dependent adaptive strategy, with localized metabolic adjustment at 100 mg/L, coordinated carbon-nitrogen reprogramming at 200 mg/L, and membrane lipid stress at 400 mg/L. Integrated metabolomics and proteomics further revealed that 200 mg/L Cr(VI) redirected carbon metabolism toward fatty acid β-oxidation and the glyoxylate cycle, promoting the production of low‑molecular‑weight organic acids (e.g., glyoxylate) associated with acidification and extracellular Cr(VI) reduction. Meanwhile, suppressed inorganic nitrogen assimilation was accompanied by enhanced branched‑chain amino acid catabolism and transamination, supporting redox homeostasis and stress adaptation. These findings demonstrate that P. oxalicum SL2 coordinated carbon-derived reductant production and nitrogen-regulated redox balance to sustain Cr(VI) detoxification, providing mechanistic insights into fungal-based Cr(VI) bioremediation.