Enhanced enantioselectivity of Bacillus coagulans in the hydrolysis of 1,2-O-isopropylidene glycerol esters by thermal knock-out of undesired enzymes

Romano, Diego; Falcioni, Francesco; Mora, Diego; Molinari, Francesco; Buthe, Andreas; Ansorge‐Schumacher, Marion B.

doi:10.1016/j.tetasy.2004.12.021

Cited by 22 publications

(18 citation statements)

References 11 publications

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“…Molinari et al showed that the CesA from B. coagulans hydrolyzed IPG caprylate esters producing (S)-IPG with 94% enantiomeric excess at 23% conversion, corresponding to an E value of 43. [15,16] Although the YbfF selectivity towards substrate 3 is high enough for practical applications, further improvement might still be possible. A plausible approach would pass by promoting a second round of mutagenesis in an iterative manner, according to the iterative saturation mutagenesis approach (ISM) described by Reetz.…”

Section: Molecular Docking Of (R)-ipg-c4 (R-1) (A) (S)-ipg-c4 (S-1mentioning

confidence: 99%

An Esterase with Superior Activity and Enantioselectivity towards 1,2‐O‐Isopropylideneglycerol Esters Obtained by Protein Design

et al. 2012

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Abstract:The Escherichia coli esterase YbfF displays high activity towards 1,2-O-isopropylideneglycerol (IPG) butyrate and IPG caprylate, and prefers the R-enantiomer of these substrates, producing the Senantiomer of the IPG product in excess. To improve the potential of the enzyme for the kinetic resolution of racemic esters of IPG, an enhancement of the activity and enantioselectivity would be highly desirable. Molecular docking of the R-enantiomer of both IPG esters into the active site of YbfF allowed the identification of proximal YbfF active site residues. Four residues (25, 124, 185 and 235) were selected as targets for mutagenesis, in order to enhance YbfF activity and enantioselectivity towards IPG esters. Random mutagenesis at positions 25, 124, 185 and 235 yielded several best YbfF variants with enhanced activity and enantioselectivity towards IPG esters. The best YbfF mutant, W235I, exhibited a 2-fold higher enantioselectivity than wild-type YbfF, with an E = 38 for IPG butyrate and an E = 77 for IPG caprylate. Molecular docking experiments further support the enhanced enantioselectivity shown experimentally and the structural effects of this amino acid substitution on the active site of YbfF are provided. The engineered W235I mutant is an attractive catalyst for practical applications in the kinetic resolution of IPG esters.

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Section: Molecular Docking Of (R)-ipg-c4 (R-1) (A) (S)-ipg-c4 (S-1mentioning

confidence: 99%

An Esterase with Superior Activity and Enantioselectivity towards 1,2‐O‐Isopropylideneglycerol Esters Obtained by Protein Design

et al. 2012

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“…Some recent papers deal with ester microbial hydrolysis (Kristová et al 2005;Romano et al 2005) but to the best of our knowledge, such a reaction has not been yet applied to acylated nucleosides. In this work, we report the results obtained in a primary screening for the microbial hydrolysis of a set of acetylated nucleosides.…”

Section: Introductionmentioning

confidence: 99%

Microbial Hydrolysis of Acetylated Nucleosides

et al. 2006

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Section: Methodsmentioning

confidence: 99%

“…30,No. 7 4 9.6 37.5Ϯ6.4 GEFA-C 6 8.2 158.2Ϯ12.5 GEFA-C 8 7.2 58.0Ϯ11.4 GEFA-C 10 6.5 52.6Ϯ3.3 GEFA-C 12 5.3 27.2Ϯ6.8 GEFA-C 18 4.1 9.7Ϯ3.9…”

Section: Screening Test For Effective Enhancersmentioning

confidence: 99%

“…Glyceryl monoethylate (GEFA-C 2 ), glyceryl monobutylate (GEFA-C 4 ) and glyceryl monocaproate (GEFA-C 6 ) were synthesized in our laboratory according to previous reports. [10][11][12][13][14] All other solvents and reagents were commercial products of analytical grade and were used without further purification.Skin Permeation Studies The full-thickness dorsal skin of male hairless mice (5-10 weeks), sacrificed by ether, was excised, and adherent fat and other visceral debris were removed from the undersurface. In vitro permeation studies were carried out with Franz diffusion cells (Vertical diffusion cell TM , Hanson Research Corporation, CA, U.S.A.) at 32°C.…”

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confidence: 99%

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Effect of Permeation Enhancers on the in Vitro Percutaneous Absorption of Pentazocine1)

Furuishi

Oda

Saito

et al. 2007

Biological & Pharmaceutical Bulletin

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The transdermal drug delivery system (TDDS) has some advantages as an alternative dosage form (i) avoiding firstpass metabolism, (ii) easy discontinuation of administration, and (iii) reduced side effects; however, the stratum corneum, which is the outermost layer of skin, provides a primary barrier to transdermal drug delivery.Pentazocine (PTZ), a relatively short-acting narcotic-antagonist analgesic, is used clinically for the relief of cancerrelated or postoperative pain, and PTZ shows an analgesic effect, a third as strong as morphine. As PTZ has a short halflife of 2 to 3 h 2) and undergoes extensive first-pass metabolism in the liver, conventional therapy with tablets or injection may result in unstable plasma concentration of the drug, which results in the induction of unexpected side effects. Long-term delivery of PTZ is thus needed at a controlled rate in the body for chronic pain management.3) Mandal et al. have reported the percutaneous absorption of PTZ together with isopropyl myristate (IPM) as an enhancer, 4,5) however, the enhanced skin permeation of PTZ is considered limited when IPM is used alone, and increased concentration of the enhancer would cause skin irritation.6) It is well known that the combination of various enhancers improved the percutaneous absorption of drugs much greater than either enhancer alone. 7,8) Regarding opioid analgesics, Morimoto et al. have reported that the percutaneous absorption of morphine hydrochloride was improved with a combination of l-menthol and ethanol. The cumulative amount of morphine permeated through hairless rat skin over 10 h was 5-fold times higher than the sum of those with 40% ethanol alone and l-menthol alone. 9)In the present study, therefore, we tried to improve the percutaneous absorption of PTZ using a combination of various enhancers. The skin permeation of PTZ through hairless mouse skin as a model membrane was determined using Franz diffusion cells and to select an appropriate enhancer for developing a new transdermal system. The flux, lag time and cumulative amount of permeated PTZ were measured as indicators of skin permeation improvement. Moreover, the effects of the structure of enhancers and hydrophiliclipophilic balance (HLB) on permeation rates of PTZ were discussed. MATERIALS AND METHODSMaterials PTZ was purchased from Kobayashi Kako Co., Ltd. (Fukui, Japan). IPM, citric acid, urea, and 1-octadecanol were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). N-Methyl-2-pyrrolidone (Pharmasolve ® , Japanese Pharmaceutical Excipient grade) was a gift from ISP Japan (Tokyo, Japan). Glyceryl monocaprylate (GEFA-C 8 , Sunsoft ® 700P-2), glyceryl monocaprate (GEFA-C 10 , Sunsoft ® 760), glyceryl monolaurate (GEFA-C 12 , Sunsoft ® 750), gylceryl monostearete (GEFA-C 18 , Sunsoft ® 8000V) and glyceryl dicaprylate (GEFA-DiC 8 , Sunsoft ® GDC-S) were a gift from Taiyo Kagaku Co., Ltd. (Mie, Japan). Glyceryl tricaprylate (GEFA-TriC8, Panacate ® 800) and polyoxyethylene laurylether (NONION K-204) were a gift from NOF Corporation (T...

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Enhanced enantioselectivity of Bacillus coagulans in the hydrolysis of 1,2-O-isopropylidene glycerol esters by thermal knock-out of undesired enzymes

Cited by 22 publications

References 11 publications

An Esterase with Superior Activity and Enantioselectivity towards 1,2‐O‐Isopropylideneglycerol Esters Obtained by Protein Design

An Esterase with Superior Activity and Enantioselectivity towards 1,2‐O‐Isopropylideneglycerol Esters Obtained by Protein Design

Microbial Hydrolysis of Acetylated Nucleosides

Effect of Permeation Enhancers on the in Vitro Percutaneous Absorption of Pentazocine1)

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