Efficient synthesis of (S)-epichlorohydrin in high yield by cascade biocatalysis with halohydrin dehalogenase and epoxide hydrolase mutants

Xue, Feng; Liu, Zhi‐Qiang; Wang, Ya‐Jun; Zhu, Hang-Qin; Wan, Nan‐Wei; Zheng, Yu‐Guo

doi:10.1016/j.catcom.2015.09.025

Cited by 21 publications

(9 citation statements)

References 25 publications

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“…In the past few decades, a number of HHDHs have been recognized as useful tools for the production of pharmaceutical intermediates and the biodegradation of toxic chlorinated organic compounds. HHDH has been proven to be a valuable alternative to chemical catalysts now used to dehalogenate halohydrins to produce epoxides …”

Section: Introductionmentioning

confidence: 99%

Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor

Zou

Zheng

2018

Biotechnology Progress

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Halohydrin dehalogenase (HHDH)-mediated dehalogenation of 1,3-dichloro-2-propanol (1,3-DCP) is a key step in the chemoenzymatic synthesis of epichlorohydrin (ECH) from glycerol. In this study, a covalent immobilization strategy was employed to enhance the stability of Agrobacterium tumefaciens HHDH using epoxy resin ES-103B as a carrier. Under optimal conditions, the activity recovery of ES-103B-immobilized HHDH (HHDH@ES-103B) was 62.4% and the specific activity was 1604 U/g. The HHDH@ES-103B exhibited excellent thermostability, with a half-life of 68.6 days at 40°C, which is 8.0-times higher than that of the free HHDH. A semicontinuous biotransformation of 1,3-DCP to ECH was performed using HHDH@ES-103B as biocatalyst in a recirculating packed bed reactor (RPBR), resulting in an ECH yield of 94.2%, with an average productivity of 5.2 g/L/h. The RPBR system exhibited a high operational stability and even after 50 cycles of reaction, it retained > 90% of the initial conversion. Furthermore, an integrated bioprocess based on in situ product recovery (ISPR) was developed in RPBR to overcome product inhibition. The integrated bioreactor equipped with an external macroporous adsorption resin HZD-9 column led to another 1.6-fold increase in ECH productivity to 8.46 g/L/h. This improved stability and reusability of HHDH@ES-103B demonstrated its potential for the biotransformation of 1,3-DCP to ECH. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:784-792, 2018.

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Section: Introductionmentioning

confidence: 99%

Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor

Zou

Zheng

2018

Biotechnology Progress

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“…This high yield demonstrated that this method was an effective way to eliminate product inhibition. Alternatively, halohydrin dehalogenases insensitive to product inhibition have been described [85,91,92]. Thus, S-ECH was produced in good enantiomeric excess (92.3% ee) and 92% yield, using a HheC mutant (Table 2, entry 2.4) [91].…”

Section: Enzymatically Catalyzed Synthesis Of Echmentioning

confidence: 99%

“…Alternatively, halohydrin dehalogenases insensitive to product inhibition have been described [85,91,92]. Thus, S-ECH was produced in good enantiomeric excess (92.3% ee) and 92% yield, using a HheC mutant (Table 2, entry 2.4) [91]. Improved ee (99%) and similar yield (92%) were achieved by using halohydrin dehalogenases (HHDHs) coupled to epoxide hydrolases (EH) ( Table 2, entry 2.5) [91].…”

Section: Enzymatically Catalyzed Synthesis Of Echmentioning

confidence: 99%

“…Thus, S-ECH was produced in good enantiomeric excess (92.3% ee) and 92% yield, using a HheC mutant (Table 2, entry 2.4) [91]. Improved ee (99%) and similar yield (92%) were achieved by using halohydrin dehalogenases (HHDHs) coupled to epoxide hydrolases (EH) ( Table 2, entry 2.5) [91]. The production of ECH was also described by using a novel HHDHTm, from Tistrella mobilis ZJB1405 (cloned and over-expressed in E. coli), with a 75% yield, but with low enantioselectivity compared to other reported HHDHs ( Table 2, entry 2.1) [92].…”

Section: Enzymatically Catalyzed Synthesis Of Echmentioning

confidence: 99%

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Preparation and Uses of Chlorinated Glycerol Derivatives

et al. 2020

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Crude glycerol (C3H8O3) is a major by-product of biodiesel production from vegetable oils and animal fats. The increased biodiesel production in the last two decades has forced glycerol production up and prices down. However, crude glycerol from biodiesel production is not of adequate purity for industrial uses, including food, cosmetics and pharmaceuticals. The purification process of crude glycerol to reach the quality standards required by industry is expensive and dificult. Novel uses for crude glycerol can reduce the price of biodiesel and make it an economical alternative to diesel. Moreover, novel uses may improve environmental impact, since crude glycerol disposal is expensive and dificult. Glycerol is a versatile molecule with many potential applications in fermentation processes and synthetic chemistry. It serves as a glucose substitute in microbial growth media and as a precursor in the synthesis of a number of commercial intermediates or fine chemicals. Chlorinated derivatives of glycerol are an important class of such chemicals. The main focus of this review is the conversion of glycerol to chlorinated derivatives, such as epichlorohydrin and chlorohydrins, and their further use in the synthesis of additional downstream products. Downstream products include non-cyclic compounds with allyl, nitrile, azide and other functional groups, as well as oxazolidinones and triazoles, which are cyclic compounds derived from ephichlorohydrin and chlorohydrins. The polymers and ionic liquids, which use glycerol as an initial building block, are highlighted, as well.

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“…Protein engineering of HheC was also performed in a study by Xue et al ( 2015b ) to increase the enzyme’s enantioselectivity in the synthesis of ( S )-epichlorohydrin starting from prochiral 1,3-dichloropropanol. Upon single site-saturation mutagenesis of several active-site residues, mutations P175S and W249P were found to exert the desired effect.…”

Section: Protein Engineeringmentioning

confidence: 99%

Recent advances on halohydrin dehalogenases—from enzyme identification to novel biocatalytic applications

Schallmey

2016

Appl Microbiol Biotechnol

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Halohydrin dehalogenases are industrially relevant enzymes that catalyze the reversible dehalogenation of vicinal haloalcohols with formation of the corresponding epoxides. In the reverse reaction, also other negatively charged nucleophiles such as azide, cyanide, or nitrite are accepted besides halides to open the epoxide ring. Thus, novel C-N, C-C, or C-O bonds can be formed by halohydrin dehalogenases, which makes them attractive biocatalysts for the production of various β-substituted alcohols. Despite the fact that only five individual halohydrin dehalogenase enzyme sequences have been known until recently enabling their heterologous production, a large number of different biocatalytic applications have been reported using these enzymes. The recent characterization of specific sequence motifs has facilitated the identification of novel halohydrin dehalogenase sequences available in public databases and has largely increased the number of recombinantly available enzymes. These will help to extend the biocatalytic repertoire of this enzyme family and to foster novel biotechnological applications and developments in the future. This review gives a general overview on the halohydrin dehalogenase enzyme family and their biochemical properties and further focuses on recent developments in halohydrin dehalogenase biocatalysis and protein engineering.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-016-7750-y) contains supplementary material, which is available to authorized users.

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Efficient synthesis of (S)-epichlorohydrin in high yield by cascade biocatalysis with halohydrin dehalogenase and epoxide hydrolase mutants

Cited by 21 publications

References 25 publications

Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor

Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor

Preparation and Uses of Chlorinated Glycerol Derivatives

Recent advances on halohydrin dehalogenases—from enzyme identification to novel biocatalytic applications

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