Multi-Enzyme Nanoparticle-Assisted Stable Isotope Incorporation Into Small Molecules by Channeling
AssigneeThe Government of the United States of America, as represented by the Secretary of the Navy
InventorsIgor L. Medintz, Joyce C. Breger, Gregory A. Ellis, Kirk Malone, Nigel Scrutton
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Abstract
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 (CHMO3M).
Claims13
A method of incorporating a radioisotope into a product molecule comprises:
- providing a nanoparticle attached to a plurality of enzymes configured as an enzymatic cascade such that a product of a first enzyme is a substrate of the second enzyme and so forth;
- providing a radioisotope source and a source substrate to the enzymatic cascade;
- and
- allowing the enzymatic cascade to act on the radioisotope source and the source substrate, thereby transferring a radioisotope from the radioisotope source into a product molecule.
A method of incorporating deuterium into (+)-dihydrocarvide comprising:
- providing a nanoparticle attached to two enzymes, namely (a) pentaerythritol tetranitrate reductase (PETNR) and (b) flavin-dependent cyclohexanone monooxygenase (CHMO);
- contacting the nanoparticle with carvone and one or more deuterium sources;
- and
- allowing the enzymes to act on the carvone and the one or more deuterium sources, thereby producing deuterated dihydrocarvide,
- wherein the one or more deuterium sources comprise deuterated water. deuterated nicotinamide adenine dinucleotide phosphate, or a combination thereof.
A method of incorporating deuterium into cinnamyl alcohol comprising:
- providing a nanoparticle attached to three enzymes, namely (a) phenylalanine ammonia lyase (PAL), (b) carboxylic acid reductase (CAR), and (c) alcohol dehydrogenase (ADH);
- contacting the nanoparticle with phenylalanine and one or more deuterium sources;
- and
- allowing the enzymes to act on the phenylalanine and the one or more deuterium sources, thereby producing deuterated cinnamyl alcohol, wherein
- the one or more deuterium sources comprise deuterated nicotinamide adenine dinucleotide phosphate, deuterated reduced nicotinamide adenine dinucleotide, or a combination thereof.
Dependencies are inferred from the claim text.