This invention relates generally to methods and compositions for producing a sesquiterpene alcohol comprising contacting a sesquiterpene with a P450 polypeptide with monooxygenase activity.

This invention relates to mutant enzymes with enhanced properties and processes for oxidation of organic compound substrates using such enzymes.

A cell line includes a genetic modification at a genetic locus that affects metabolism of a drug in a manner similar to a human subject having a genotype that affects metabolism of the drug. A method for making such a cell line generally includes identifying a locus and allelic variants at the locus in a human that affect metabolism of the drug, providing a parental cell line that comprises the locus that affects metabolism of the drug in the human subject, and introducing a genetic modification into the parental cell at the locus, thereby forming a variant cell line comprising an allelic variant at the locus having the genetic modification.

Compositions and methods for treating hypertension in a subject are provided, including administering an antisense oligomer effective to reduce expression of cytochrome P450 3A5 (CYP3A5) enzyme. The antisense oligomer includes phosphorodiamidate morpholino oligonucleotide (PMO), phosphorothioate 2-O-methyl oligoribonucleotides (PSO), locked nucleic acid nucleotide, locked nucleic acid analog nucleotide, or another modified oligonucleotide backbone or nuclease-resistant backbone. The antisense oligomer is administered transdermally, subcutaneously, or orally, and optionally with a pharmaceutically acceptable carrier. In one embodiment, the antisense oligomer is an oligomer that is antisense to mRNAs that encode CYP3A5, for instance targeted at the AUG start site of the mRNAs that encode CYP3A5 or at a G4 structure within CYP3A5.

Provided are mucolytic compounds that are more effective, and/or absorbed less rapidly from mucosal surfaces, and/or are better tolerated as compared to N-acetylcysteine (NAC) and DTT. The compounds are represented by compounds of Formula I which embrace structures (Ia)-(Ib): ##STR00001##
where the structural variables are as defined herein.

The present invention provides improved P450-BM3 variants with improved activity. In some embodiments, the P450-BM3 variants exhibit improved activity over a wide range of substrates.

Provided are a cytochrome P450 (CYP716A53v2) mutant protein and the use thereof. The mutation is mutated at a site selected from the group consisting of F167V, T451A, I117S and L208C or a combination thereof on the basis of a wild-type CYP716A53v2 protein. The enzyme catalytic activity of the CYP716A53v2 mutant obtained after mutation is improved, and the yield of panaxatriol can be improved.

The present disclosure relates to cytochrome P450 monooxygenases capable of oxidizing a monoterpenoid indole alkaloid (MIA) substrate and methods and uses thereof. The substrate may be a camptothecinoid, an evodiaminoid or an ellipticinoid. The disclosure further relates to method of producing hydroxylated monoterpenoid indole alkaloids, as well as derivatives and analogues of the produced hydroxylated monoterpenoid indole alkaloids. Pharmaceutical compositions comprising the hydroxylated monoterpenoid indole alkaloid derivatives are also provided.

The disclosed compositions, methods, and systems are useful in treating and preventing various cancers associated with buildup of mitochondrial cholesterol. In many embodiments, the disclosed compositions, methods, and systems may improve the efficacy and cytotoxicity of chemotherapeutic compounds, for example increasing cellular sensitivity to chemotherapy and/or reducing or preventing resistance. In many embodiments, the cancer may be early or late stage hepatocellular carcinoma.

The disclosure generally relates to the fields of synthetic organic chemistry. In particular, the present disclosure relates to methods and systems for the imidation of sulfides.