82177-86-4

Upstream product

• 822-12-8 sodium myristoate 
• 544-63-8 n-tetradecanoic acid 

Relevant academic research and scientific papers

Novel insights into oxidation of fatty acids and fatty alcohols by cytochrome P450 monooxygenase CYP4B1

CYP4B1 is an enigmatic mammalian cytochrome P450 monooxygenase acting at the interface between xenobiotic and endobiotic metabolism. A prominent CYP4B1 substrate is the furan pro-toxin 4-ipomeanol (IPO). Our recent investigation on metabolism of IPO related compounds that maintain the furan functionality of IPO while replacing its alcohol group with alkyl chains of varying structure and length revealed that, in addition to cytotoxic reactive metabolite formation (resulting from furan activation) non-cytotoxic ω-hydroxylation at the alkyl chain can also occur. We hypothesized that substrate reorientations may happen in the active site of CYP4B1. These findings prompted us to re-investigate oxidation of unsaturated fatty acids and fatty alcohols with C9–C16 carbon chain length by CYP4B1. Strikingly, we found that besides the previously reported ω- and ω-1-hydroxylations, CYP4B1 is also capable of α-, β-, γ-, and δ-fatty acid hydroxylation. In contrast, fatty alcohols of the same chain length are exclusively hydroxylated at ω, ω-1, and ω-2 positions. Docking results for the corresponding CYP4B1-substrate complexes revealed that fatty acids can adopt U-shaped bonding conformations, such that carbon atoms in both arms may approach the heme-iron. Quantum chemical estimates of activation energies of the hydrogen radical abstraction by the reactive compound 1 as well as electron densities of the substrate orbitals led to the conclusion that fatty acid and fatty alcohol oxidations by CYP4B1 are kinetically controlled reactions.

The CYPome of sorangium cellulosum so ce56 and identification of CYP109D1 as a new fatty acid hydroxylase

The first systematic study of the complete cytochrome P450 complement (CYPome) of Sorangium cellulosum So ce56, which is a producer of important secondary metabolites and has the largest bacterial genome sequenced to date, is presented. We describe the bioinformatic analysis of the So ce56 cytochrome P450 complement consisting of 21 putative P450 genes. Because fatty acids play a pivotal role during the complex life cycle of myxobacteria, we focused our studies on the characterization of fatty acid hydroxylases. Three novel potential fatty acid hydroxylases (CYP109D1, CYP264A1, and CYP266A1) were used for detailed characterization. One of them, CYP109D1 was able to perform subterminal hydroxylation of saturated fatty acids with the support of two autologous and one heterologous electron transfer system(s). The kinetic parameters for the product hydroxylation were derived.

Facile determination of the absolute stereochemistry of hydroxy fatty acids by GC: application to the analysis of fatty acid oxidation by a P450BM3 mutant

The determination of the absolute stereochemistry of hydroxy fatty acid methyl esters as their (S)-ibuprofen esters is possible via standard gas chromatographic techniques. Analyses of various racemic and nonracemic standards and mixtures from enzymic oxi

Catalytic hydroxylation in biphasic systems using CYP102A1 mutants

Cytochrome P450 monooxygenases are biocatalysts that hydroxylate or epoxidise a wide range of hydrophobic organic substrates. Their technical application is, however, limited to a small number of whole-cell processes. The use of the isolated P450 enzymes is believed to be impractical due to their low stability, stoichiometric need of the expensive cofactor NAD(P)H and low solubility of most substrates in aqueous media. We investigated the behaviour of an isolated bacterial monooxygenase (mutants of CYP102A1) in a biphasic reaction system supported by cofactor recycling with the NADP +-dependent formate dehydrogenase from Pseudomonas sp 101. Using this experimental set-up cyclohexane, octane and myristic acid were hydroxylated. To reduce the process costs a novel NADH-dependent mutant of CYP102A1 was designed. For recycling of NADH an NAD+-dependent FDH was used. The stability of the monooxygenase mutants under the reaction conditions in the biphasic system was quite high as revealed by total turnover numbers of up to 12,850 in the NADPH-dependent cyclohexane hydroxylation and up to 30,000 in the NADH-dependent myristic acid oxidation.

Regioselectivity and Activity of Cytochrome P450 BM-3 and Mutant F87A in Reactions Driven by Hydrogen Peroxide

Cytochrome P450 BM-3 (EC 1.14.14.1) is a monooxygenase that utilizes NADPH and dioxygen to hydroxylate fatty acids at subterminal positions. The enzyme is also capable of functioning as a peroxygenase in the same reaction, by utilizing hydrogen peroxide i