638-26-6Relevant academic research and scientific papers
Biocatalytic production of 10-hydroxystearic acid, 10-ketostearic acid, and their primary fatty amides
Kuo, Tsung Min,Levinson, William E.
, p. 671 - 675 (2006)
The objective of this study was to develop scaleup bioprocesses for producing 10-hydroxystearic acid (10-HSA) and 10-ketostearic acid (10-KSA) as well as their primary amides for potential new uses. A reactor process was examined to obtain the mono-oxygenated FA using Sphingobacterium thalpophilum (NRRL B-14797) and Bacillus sphaericus (NRRL NRS-732), which solely produce 10-HSA and 10-KSA, respectively, from technical-grade oleic acid. By using an 8-h-old B-14797 culture grown in a manganese-containing WF6 medium, pH 7.3, at 28°C under 350 rpm agitation and 0-50% dissolved oxygen concentrations provided by a controlled sparger aeration, the production of 10-HSA reached 7 g/L with a 40% yield in 4 d. In using a 12-h-old NRS-732 culture grown in a pyruvate-containing PF6 medium, pH 6.5, at 30°C under 750 rpm agitation without any sparger aeration during the conversion reaction, 10-KSA production reached 7.9 g/L with a yield of more than 54% in 72 h. The scaleup reactor process provided crystalline 10-HSA and 10-KSA for producing new primary amides via a lipase-catalyzed amidation reaction with yields of 94 and 92%, respectively. The primary amides of 10-HSA and 10-KSA displayed m.p. of 115 and 120°C, respectively. Copyright
Rational Engineering of Hydratase from Lactobacillus acidophilus Reveals Critical Residues Directing Substrate Specificity and Regioselectivity
Eser, Bekir Engin,Poborsky, Michal,Dai, Rongrong,Kishino, Shigenobu,Ljubic, Anita,Takeuchi, Michiki,Jacobsen, Charlotte,Ogawa, Jun,Kristensen, Peter,Guo, Zheng
, p. 550 - 563 (2019/11/25)
Enzymatic conversion of fatty acids (FAs) by fatty acid hydratases (FAHs) presents a green and efficient route for high-value hydroxy fatty acid (HFA) production. However, limited diversity was achieved among HFAs, to date, with respect to chain length and hydroxy position. In this study, two highly similar FAHs from Lactobacillus acidophilus were compared: FA-HY2 has a narrow substrate scope and strict regioselectivity, whereas FA-HY1 utilizes longer chain substrates and hydrates various double-bond positions. It is revealed that three active-site residues play a remarkable role in directing substrate specificity and regioselectivity of hydration. If these residues on FA-HY2 are mutated to the corresponding ones in FA-HY1, a significant expansion of substrate scope and a distinct enhancement in hydration of double bonds towards the ω-end of FAs is observed. A three-residue mutant of FA-HY2 (TM-FA-HY2) displayed an impressive reversal of regioselectivity towards linoleic acid, shifting the ratio of the HFA regioisomers (10-OH/13-OH) from 99:1 to 12:88. Notable changes in regioselectivity were also observed for arachidonic acid and for C18 polyunsaturated fatty acid substrates. In addition, TM-FA-HY2 converted eicosapentaenoic acid into its 12-hydroxy product with high conversion at the preparative scale. Furthermore, it is demonstrated that microalgae are a source of diverse FAs for HFA production. This study paves the way for tailor-made FAH design to enable the production of diverse HFAs for various applications from the polymer industry to medical fields.
Rhodococcus erythropolis Oleate Hydratase: a New Member in the Oleate Hydratase Family Tree—Biochemical and Structural Studies
Lorenzen, Jan,Driller, Ronja,Waldow, Ayk,Qoura, Farah,Loll, Bernhard,Brück, Thomas
, p. 407 - 414 (2017/12/13)
Recently, the enzyme family of oleate hydratases (OHs: EC 4.2.1.53) has gained increasing scientific and economic interest, as these FAD-binding bacterial enzymes do not require cofactor recycling and possess high thermal and pH stability. Their products, hydroxy fatty acids, are used in specialty chemical applications including surfactant and lubricant formulations. The “oleate hydratase engineering database”, established by Schmid et al. (2017), divides all OHs into 11 families (HFam1 to 11). To date, only two crystal structures of homodimeric OHs from the families HFam2 and HFam11 have been reported. In this study, we biophysically characterized an OH belonging to the HFam3 family, originating from the marine bacterium Rhodococcus erythropolis, for the first time. The crystal structure revealed that this new OH (OhyRe) surprisingly is a monomer in its active form. This particular feature provides new avenues for enzyme engineering and recycling through immobilization.
METHOD FOR PRODUCING OPTICALLY ACTIVE HYDROXY FATTY ACID
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Paragraph 0117; 0126-0127, (2017/07/23)
PROBLEM TO BE SOLVED: To provide a means for producing optically active hydroxy fatty acid applicable to product materials having various structures, also having low production cost and high stereoselectivity. SOLUTION: Provided is a method for producing a compound represented by formula (I-1), including: a carbon chain connection step; the second oxidation step; a stereoselective reduction step; and the third oxidation step. Also provided is a method for producing a compound represented by formula (I-2), including: a carbon chain connection step; a speed theoretical optical resolution step; and the third oxidation step. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
Biocatalytic study of novel oleate hydratases
Schmid, Jens,Steiner, Lisa,Fademrecht, Silvia,Pleiss, Jürgen,Otte, Konrad B.,Hauer, Bernhard
, p. S243 - S249 (2019/04/02)
The direct hydration of C[dbnd]C bonds to yield alcohols or the reverse dehydration is chemically challenging but highly sought after. Recently, oleate hydratases (OAHs) gained attention as biocatalytic alternatives capable of hydrating isolated, non-activated C[dbnd]C bonds. Their natural reaction is the conversion of oleic acid to (R)-10-hydroxystearic acid. In this work, we report the first comparative study of several OAHs. Therefore we established the Hydratase Engineering Database (HyED) comprising 2046 putative OAHs from eleven homologous families and selected nine homologs for cloning in E. coli. The heterologously expressed enzymes were evaluated concerning activity and substrate specificity. The enzymes have a broad substrate scope ranging from oleic acid (C18) to the novel synthetic substrate (Z)-undec-9-enoic acid (C11). The OAHs from Elizabethkingia meningoseptica and Chryseobacterium gleum showed the best expression, highest stability and broadest substrate scope, making them interesting candidates for directed evolution to engineer them for the application as general hydratase catalysts.
Configurational Assignment of ‘Cryptochiral’ 10-Hydroxystearic Acid Through an Asymmetric Catalytic Synthesis
Brunner, Andreas,Hintermann, Lukas
, p. 928 - 943 (2016/12/09)
An asymmetric catalytic total synthesis of (S)-10-hydroxystearic acid (1) for comparison of its absolute configuration to that of samples obtained by fermentative hydration of oleic acid is reported. The synthesis involves two catalytic key-steps, namely Ru-catalyzed anti-Markovnikov hydration of 9-decynoic acid (7) to 10-oxodecanoic acid (5), followed by titanium-mediated asymmetric catalytic addition of dioctylzinc (25) to 5 in presence of the chiral ligand N,N’-((1R,2R)-cyclohexane-1,2-diyl)bis(1,1,1-trifluoromethanesulfonamide) (6). The synthesis is short and efficient and avoids use of protecting groups. Ozonolysis of 10-undecynoic acid (9) to 5 provides an alternative entry point into the synthetic route. The double dehydrobromination of (ω,ω-1)-dibromoalkanoic acids to ω-alkynoic acids under a variety of conditions was investigated with 10,11-dibromoundecanoic acid (11) as model substrate and using qNMR to quantify all reaction products. The synthetic approaches presented here have the potential to be generalized to the asymmetric catalytic synthesis of a variety of n-hydroxy-fatty acids.
Combined Biocatalytic and Chemical Transformations of Oleic Acid to ω-Hydroxynonanoic Acid and α,ω-Nonanedioic Acid
Koppireddi, Satish,Seo, Joo-Hyun,Jeon, Eun-Yeong,Chowdhury, Partha Sarathi,Jang, Hyun-Young,Park, Jin-Byung,Kwon, Yong-Uk
supporting information, p. 3084 - 3092 (2016/10/09)
A practical chemoenzymatic method for the synthesis of 9-hydroxynonanoic acid and 1,9-nonanedioic acid (i.e., azelaic acid) from oleic acid [(9Z)-octadec-9-enoic acid] was investigated. Biotransformation of oleic acid into 9-(nonanoyloxy)nonanoic acid via 10-hydroxyoctadecanoic acid and 10-keto-octadecanoic acid was driven by a C-9 double bond hydratase from Stenotrophomonas maltophilia, an alcohol dehydrogenase from Micrococcus luteus, and a Baeyer–Villiger monooxygenase (BVMO) from Pseudomonas putida KT2440, which was expressed in recombinant Escherichia coli. After production of the ester (i.e., the BVMO reaction product), the compound was chemically hydrolyzed to n-nonanoic acid and 9-hydroxynonanoic acid because n-nonanoic acid is toxic to E. coli. The ester was also converted into 9-hydroxynonanoic acid and the n-nonanoic acid methyl ester, which can be oxygenated into the 9-hydroxynonanoic acid methyl ester by the AlkBGT from P. putida GPo1. Finally, 9-hydroxynonanoic acid was chemically oxidized to azelaic acid with a high yield under fairly mild reaction conditions. For example, whole-cell biotransformation at a high cell density (i.e., 10 g dry cells/L) allowed the final ester product concentration and volumetric productivity to reach 25 mM and 2.8 mM h?1, respectively. The overall molar yield of azelaic acid from oleic acid was 58%, based on the biotransformation and chemical transformation conversion yields of 84% and 68%, respectively. (Figure presented.).
Characterization of hydroxy fatty acid dehydrogenase involved in polyunsaturated fatty acid saturation metabolism in Lactobacillus plantarum AKU 1009a
Takeuchi, Michiki,Kishino, Shigenobu,Park, Si-Bum,Kitamura, Nahoko,Ogawa, Jun
, p. 7 - 12 (2015/05/13)
Hydroxy fatty acid dehydrogenase, which is involved in polyunsaturated fatty acid saturation metabolism in Lactobacillus plantarum AKU 1009a, was cloned, expressed, purified, and characterized. The enzyme preferentially catalyzed NADH-dependent hydrogenation of oxo fatty acids over NAD+-dependent dehydrogenation of hydroxy fatty acids. In the dehydrogenation reaction, fatty acids with an internal hydroxy group such as 10-hydroxy-cis-12-octadecenoic acid, 12-hydroxy-cis-9-octadecenoic acid, and 13-hydroxy-cis-9-octadecenoic acid served as better substrates than those with α- or β-hydroxy groups such as 3-hydroxyoctadecanoic acid or 2-hydroxyeicosanoic acid. The apparent Km value for 10-hydroxy-cis-12-octadecenoic acid (HYA) was estimated to be 38 μM with a kcat of 7.6 × 10-3 s-1. The apparent Km value for 10-oxo-cis-12-octadecenoic acid (KetoA) was estimated to be 1.8 μM with a kcat of 5.7 × 10-1 s-1. In the hydrogenation reaction of KetoA, both (R)- and (S)-HYA were generated, indicating that the enzyme has low stereoselectivity. This is the first report of a dehydrogenase with a preference for fatty acids with an internal hydroxy group.
Organic gelling agent including hydroxy stearic acid as a fatty diamide
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Paragraph 0055; 0056; 0057, (2016/10/07)
The invention is directed to a fatty acid diamide comprising in its structure specific hydroxycarboxylic acids, and to the use of this product as an organogelator or rheology agent, also known as a rheology additive, in particular in coating, glue or adhesive, molding, mastic, sealing or cosmetic compositions.
Enzymatic kinetic resolution of hydroxystearic acids: A combined experimental and molecular modelling investigation
Ebert, Cynthia,Felluga, Fulvia,Forzato, Cristina,Foscato, Marco,Gardossi, Lucia,Nitti, Patrizia,Pitacco, Giuliana,Boga, Carla,Caruana, Paolo,Micheletti, Gabriele,Calonghi, Natalia,Masotti, Lanfranco
, p. 38 - 45 (2012/11/07)
Enantioenriched 7-, 8-, 9-, and 10-hydroxystearic acids (HSA) were obtained, for the first time, by kinetic resolution of their racemates with lipases CALB and PS, in the presence of vinyl acetate. Among them, the best results were obtained for 7-HSA and 9-HSA, whose enantiomeric excess was around 55%. The same resolutions carried out on the hydroxy esters completely failed. For the acid substrates neither the Kazlauskas' rule nor the 3D-QSAR model could be applied, since both models are focused on the CALB alcohol-pocket evaluation and not on the acyl-pocket one. Therefore, a semiquantitative approach was used, whose results were in accordance with our findings, as far as the absolute configuration of the product is concerned.
