Application of Metal Oxide Nanoparticles for the Bacterial Transformation of (−)-Isopulegol

Background: The biotransformation of the monoterpenoid (−)-isopulegol by Rhodococcus rhodochrous yields valuable diol and hydroxy acid derivatives; however, the yields are moderate, and formation of the (S)-epoxide byproduct significantly reduces the overall selectivity. Metal oxide nanoparticles (NPs) can modulate biocatalytic activity; however, their effects on monoterpenoid biotransformation are poorly understood. Methods: We investigated the effects of NiO (50 mg/L) and CuO NPs (5 mg/L) on (−)-isopulegol conversion by R. rhodochrous IEGM 1362. Products were quantified by GC–MS; cellular responses were assessed using respirometry, zeta potential measurements, AFM-CLSM, TEM, SEM, EDX, and cell viability assays. Results: NiO NPs at 50 mg/L significantly increased the total yield of target compounds (diol and hydroxy acid) from 36.1% to 48.3%. Importantly, NiO suppressed the formation of the undesired (S)-epoxide. In contrast, CuO NPs (5 mg/L) completely abolished target product formation. Both NPs reduced cell respiratory activity, shifted zeta potential toward less negative values, and induced cell aggregation and ultrastructural damage. NiO NPs were adsorbed onto the cell surface. Conclusions: NiO NPs selectively enhance the yield of valuable oxygenated metabolites of (−)-isopulegol while inhibiting the competing epoxidation pathway. Conversely, CuO NPs are detrimental and unsuitable for this bioprocess.