{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:02:07Z","timestamp":1790596927084,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-14-20015"],"award-info":[{"award-number":["24-14-20015"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-14-20015"],"award-info":[{"award-number":["24-14-20015"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The biotransformation of the monoterpenoid (\u2212)-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 (\u2212)-isopulegol conversion by R. rhodochrous IEGM 1362. Products were quantified by GC\u2013MS; 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 (\u2212)-isopulegol while inhibiting the competing epoxidation pathway. Conversely, CuO NPs are detrimental and unsuitable for this bioprocess.<\/jats:p>","DOI":"10.3390\/molecules31193445","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of Metal Oxide Nanoparticles for the Bacterial Transformation of (\u2212)-Isopulegol"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6353-2975","authenticated-orcid":false,"given":"Polina Y.","family":"Maltseva","sequence":"first","affiliation":[{"name":"Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences, Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences, 13 Golev Str., 614081 Perm, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Alexandra A.","family":"Chudinova","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences, Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences, 13 Golev Str., 614081 Perm, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-5726","authenticated-orcid":false,"given":"Natalia A.","family":"Plotnitskaya","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences, Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences, 13 Golev Str., 614081 Perm, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-4789","authenticated-orcid":false,"given":"Irina B.","family":"Ivshina","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences, Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences, 13 Golev Str., 614081 Perm, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Le, T.M., B\u00e9rdi, P., Zupk\u00f3, I., F\u00fcl\u00f6p, F., and Szakonyi, Z. (2018). Synthesis and Transformation of (-)-Isopulegol-Based Chiral \u03b2-Aminolactones and \u03b2-Aminoamides. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113522"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1016\/j.bmcl.2018.04.057","article-title":"Highly Potent Activity of Isopulegol-Derived Substituted Octahydro-2H-chromen-4-ols against Influenza A and B Viruses","volume":"28","author":"Ilyina","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s10600-017-1966-7","article-title":"Influenza Antiviral Activity of Br-Containing [2R,4R(S),4\u03b1R,7R,8\u03b1R]-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ols Prepared from (\u2013)-Isopulegol","volume":"53","author":"Nazimova","year":"2017","journal-title":"Chem. Nat. Compd."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1007\/s10593-020-02753-x","article-title":"Synthesis of 1,3-Oxazine Derivatives Based on (\u2013)-Isopulegol Using the Ritter Reaction and Study of Their Analgesic Activity","volume":"56","author":"Pavlova","year":"2020","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109467","DOI":"10.1016\/j.enzmictec.2019.109467","article-title":"Cutinases as Stereoselective Catalysts: Specific Activity and Enantioselectivity of Cutinases and Lipases for Menthol and Its Analogs","volume":"133","author":"Su","year":"2020","journal-title":"Enzym. Microb. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1139\/m87-082","article-title":"Microbial Transformation of Menthol and Menthane-3,4-diol","volume":"33","author":"Shukla","year":"1987","journal-title":"Can. J. Microbiol."},{"key":"ref_7","unstructured":"Kurtboke, I. (2017). Hydrocarbon-Oxidizing Bacteria and Their Potential in Eco-Biotechnology and Bioremediation. Microbial Resources, Elsevier."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ivshina, I.B., Luchnikova, N.A., Maltseva, P.Y., Ilyina, I.V., Volcho, K.P., Gatilov, Y.V., Korchagina, D.V., Kostrikina, N.A., Sorokin, V.V., and Mulyukin, A.L. (2022). Biotransformation of (\u2013)-Isopulegol by Rhodococcus rhodochrous. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080964"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maltseva, P.Y., Plotnitskaya, N.A., Chudinova, A.A., Ilyina, I.V., Volcho, K.P., Salakhutdinov, N.F., and Ivshina, I.B. (2025). Rhodococcus rhodochrous IEGM 1362 Immobilized in Macroporous PVA Cryogel as an Effective Biocatalyst for the Production of Bioactive (\u2013)-Isopulegol Compounds. Pharmaceuticals, 18.","DOI":"10.3390\/ph18060839"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2113\/gselements.4.6.395","article-title":"Nanoparticles in the Soil Environment","volume":"4","author":"Theng","year":"2008","journal-title":"Elements"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11270-008-9797-6","article-title":"Influence of Metal Nanoparticles on the Soil Microbial Community and Germination of Lettuce Seeds","volume":"197","author":"Shah","year":"2009","journal-title":"Water Air Soil Pollut."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12302-018-0132-6","article-title":"Nanoparticles in the Environment: Where Do We Come from, Where Do We Go To?","volume":"30","author":"Bundschuh","year":"2018","journal-title":"Environ. Sci. Eur."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/19440049.2013.865147","article-title":"Synthesis, Antibacterial Activity, Antibacterial Mechanism and Food Applications of ZnO Nanoparticles: A Review","volume":"31","author":"Shi","year":"2014","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1021\/acs.langmuir.4c03987","article-title":"Adaptations of Rhodococcus rhodochrous Biofilms to Oxidative Stress Induced by Copper(II) Oxide Nanoparticles","volume":"41","author":"Kuyukina","year":"2025","journal-title":"Langmuir"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Niu, B., and Zhang, G. (2023). Effects of Different Nanoparticles on Microbes. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030542"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41467-021-27193-9","article-title":"Hydrophilic Nanoparticles That Kill Bacteria While Sparing Mammalian Cells Reveal the Antibiotic Role of Nanostructures","volume":"13","author":"Jiang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","first-page":"541","article-title":"Synthesis, Characterization and Antibacterial Activity of Colloidal NiO Nanoparticles","volume":"29","author":"Khashan","year":"2016","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1021\/nn300291r","article-title":"Dual Enzyme-like Activities of Iron Oxide Nanoparticles and Their Implication for Diminishing Cytotoxicity","volume":"6","author":"Chen","year":"2012","journal-title":"ACS Nano"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.biortech.2013.03.082","article-title":"Optimisation and Enhancement of Biohydrogen Production Using Nickel Nanoparticles\u2014A Novel Approach","volume":"141","author":"Mullai","year":"2013","journal-title":"Bioresour. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.envpol.2012.05.009","article-title":"Sub-Toxic Effects of CuO Nanoparticles on Bacteria: Kinetics, Role of Cu Ions and Possible Mechanisms of Action","volume":"169","author":"Bondarenko","year":"2012","journal-title":"Environ. Pollut."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12934-026-02936-9","article-title":"Gold Nanoparticle-Mediated Metabolic Engineering in Trichoderma longibrachiatum MD33 Unveils a Hybrid Terpenoid-Alkaloid Pathway for Enhanced Dendrobine Biosynthesis","volume":"25","author":"Sarsaiya","year":"2026","journal-title":"Microb. Cell Fact."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115988","DOI":"10.1016\/j.indcrop.2022.115988","article-title":"Molecular, Biochemical, and Metabolic Changes Induced by Gold Nanoparticles in Taxus baccata L. Cell Culture","volume":"192","author":"Golinejad","year":"2023","journal-title":"Ind. Crops Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1080\/07388551.2024.2438161","article-title":"Unveiling the Potential of Dendrobine: Insights into Bioproduction, Bioactivities, Safety, Circular Economy, and Future Prospects","volume":"45","author":"Sarsaiya","year":"2025","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.scitotenv.2018.08.386","article-title":"The Revolution of Performance, Sludge Characteristics and Microbial Community of Anammox Biogranules under Long-Term NiO NPs Exposure","volume":"649","author":"Xu","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.msec.2019.03.012","article-title":"Comparative in situ ROS Mediated Killing of Bacteria with Bulk Analogue, Eucalyptus Leaf Extract (ELE)-Capped and Bare Surface Copper Oxide Nanoparticles","volume":"100","author":"Ali","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.2166\/wst.2018.416","article-title":"Generation of Reactive Oxygen Species by Promoting the Cu(II)\/Cu(I) Redox Cycle with Reducing Agents in Aerobic Aqueous Solution","volume":"78","author":"Li","year":"2018","journal-title":"Water Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wall, J., Seleci, D.A., Schworm, F., Neuberger, R., Link, M., Hufnagel, M., Schumacher, P., Schulz, F., Heinrich, U., and Wohlleben, W. (2021). Comparison of Metal-Based Nanoparticles and Nanowires: Solubility, Reactivity, Bioavailability and Cellular Toxicity. Nanomaterials, 12.","DOI":"10.3390\/nano12010147"},{"key":"ref_28","unstructured":"Bull, S.D., Tibbetts, J.D., and Cunningham, W. (2024). Preparation of p-Menthane-3,8-diol Stereoisomers and Uses Thereof. (WO2024\/252135\/A1), WO Patent."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01864-19","DOI":"10.1128\/JCM.01864-19","article-title":"The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: Background, Organization, Functions, and Processes","volume":"58","author":"Weinstein","year":"2020","journal-title":"J. Clin. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/19\/3445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:39:33Z","timestamp":1790595573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/19\/3445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":29,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["molecules31193445"],"URL":"https:\/\/doi.org\/10.3390\/molecules31193445","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]}}}