Multi-enzyme systems attached to nanoparticles are effective to efficiently and controllably incorporate stable isotopes (such as deuterium) during the synthesis of small molecules. In one example, deuterium is incorporated into (+)-dihydrocarvide using a cascade involving the enzymes (a) pentaerythritol tetranitrate reductase (PETNR) and (b) flavin-dependent cyclohexanone monooxygenase triple variant F249A/F280A/F435A (CHMO.sub.3M).