17369-51-6Relevant articles and documents
Microbial Transformation of 12-Hydroxyoctadecanoic Acid to 5-n-Hexyl-Tetrahydrofuran-2-Acetic Acid
Huang, J.-K.,Keudell, K. C.,Zhao, J.,Klopfenstein, W. E.,Wen, L.,et al.
, p. 323 - 326 (1995)
Stationary-phase cells of a corynebacterium (FUI-2) and a bacillus (NRRL B-14864) isolate, when grown aerobically in 1percent YE medium at 25 deg C, converted 12-hydroxystearic acid to a major compound, 5-n-hexyl-tetrahydrofuran-2-acetic acid, and other intermediate and minor compounds (6-hydroxydodecanoic acid, 4-hydroxydecanoic acid, 4-ketodecanoic acid and γ-decanolactone).The yields of 5-n-hexyl-tetrahydrofuran-2-acetic acid, 4-hydroxydecanoic acid, and γ-decanolactone, by Bacillus lentus NRRL B-14864 were 43percent, 18percent and 5percent, respectively, after 2.5 d of incubation. Key Words: Bacillus lentus, corynebacterium, D-(+)-12-hydroxy-octadecanoic acid, D-(+)-12-hydroxystearic acid, γ-decanolactone, 4-hydroxydecanoic acid, 6-hydroxydodecanoic acid, 4-ketodecanoic acid, 5-n-hexyl-tetrahydrofuran-2-acetic acid.
Novel insights into oxidation of fatty acids and fatty alcohols by cytochrome P450 monooxygenase CYP4B1
Thesseling, Florian A.,Hutter, Michael C.,Wiek, Constanze,Kowalski, John P.,Rettie, Allan E.,Girhard, Marco
, (2019/12/12)
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.