Abstract
The aim of this study is to summarize the current progress in the design of biocatalytic processes applicable for the production of optically pure mandelic acids and their analogues. These compounds are used as building blocks for pharmaceutical chemistry and as chiral resolving agents. Their enzymatic syntheses mainly employed nitrile hydrolysis with nitrilases, ester hydrolysis, ammonolysis or esterification with lipases or esterases, and ketone reduction or alcohol oxidation with dehydrogenases. Each of these methods will be characterized in terms of its product concentrations, enantioselectivities, and the types of catalysts used. This review will focus on the dynamic kinetic resolution of mandelonitrile and analogues by nitrilases resulting in the production of high concentrations of (R)-mandelic acid or (R)-2-chloromandelic acid with excellent e.e. Currently, there is no comparable process for (S)-mandelic acids. However, the coupling of the S-selective cyanation of benzaldehyde with the enantioretentive hydrolysis of (S)-mandelonitrile thus obtained is a promising strategy. The major product can be changed from (S)-acid to (S)-amide using nitrilase mutants. The competitiveness of the biocatalytic and chemical processes will be assessed. This review covers the literature published within 2003–2017.
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References
Blacker AJ, Houson IN (2002) Preparation of mandelic acid derivatives. Patent WO2002066410A1 (29. 8. 2002)
Cao Y, Wu SS, Li JH, Wu B, He BF (2014) Highly efficient resolution of mandelic acid using lipase from Pseudomonas stutzeri LC2-8 and a molecular modeling approach to rationalize its enantioselectivity. J Mol Catal B-Enzym 99:108–113. https://doi.org/10.1016/j.molcatb.2013.10.026
Chen S, Liu FY, Zhan K, Huang HS, Wang HN, Zhou JY, Zhang J, Gong YW, Zhang DL, Chen YP, Lin C, Wang B (2016) An efficient enzymatic aminolysis for kinetic resolution of aromatic α-hydroxyl acid in non-aqueous media. Tetrahedron Lett 57(48):5312–5314. https://doi.org/10.1016/j.tetlet.2016.10.054
Chmura A, Rustler S, Paravidino M, van Rantwijk F, Stolz A, Sheldon RA (2013) The combi-CLEA approach: enzymatic cascade synthesis of enantiomerically pure (S)-mandelic acid. Tetrahedron-Asymmetry 24(19):1225–1232. https://doi.org/10.1016/j.tetasy.2013.08.013
Gong JS, Li H, Lu ZM, Shi JS, Xu ZH (2012) Recent progress in the application of nitrilase in the biocatalytic synthesis of pharmaceutical intermediates. Prog Chem 27(4):448–458. https://doi.org/10.7536/PC141113
Guo F, Ye LD, Li AP, Yan XH, Yang CC, Yu HW (2016) Insight into the role of halogen bond in the activity of D-mandelate dehydrogenase toward halogenated substrates. Tetrahedron Lett 57(18):1944–1948. https://doi.org/10.1016/j.tetlet.2016.03.001
He YC, Ma CL, Zhang X, Li L, Xu JH, Wu MX (2013) Highly enantioselective oxidation of racemic phenyl-1,2-ethanediol to optically pure (R)-(−)-mandelic acid by a newly isolated Brevibacterium lutescens CCZU12-1. Appl Microbiol Biotechnol 97(16):7185–7194. https://doi.org/10.1007/s00253-013-4989-4
Jiang XP, Lu TT, Liu CH, Ling XM, Zhuang MY, Zhang JX, Zhang YW (2016) Immobilization of dehydrogenase onto epoxy-functionalized nanoparticles for synthesis of (R)-mandelic acid. Int J Biol Macromol 88:9–17. https://doi.org/10.1016/j.ijbiomac.2016.03.031
Ju X, Yu HL, Pan J, Wei DZ, Xu JH (2010) Bioproduction of chiral mandelate by enantioselective deacylation of α-acetoxyphenylacetic acid using whole cells of newly isolated Pseudomonas sp. ECU1011. Appl Microbiol Biotechnol 86(1):83–91. https://doi.org/10.1007/s00253-009-2286-z
Kaplan O, Veselá AB, Petříčková A, Pasquarelli F, Pičmanová M, Rinágelová A, Bhalla TC, Pátek M, Martínková L (2013) A comparative study of nitrilases identified by genome mining. Mol Biotechnol 54(3):996–1003. https://doi.org/10.1007/s12033-013-9656-6
Kaul P, Banerjee A, Banerjee UC, Nitrile hydrolases in: Polaina J, Mac Cabe AP (Eds.): Industrial enzymes: structure, function and applications. Springer Dordrecht 2007, pp. 531–547
Li GY, Huang KL, Jiang YR, Ding P (2007) Production of (R)-mandelic acid by immobilized cells of Saccharomyces cerevisiae on chitosan carrier. Process Biochem 42(10):1465–1469. https://doi.org/10.1016/j.procbio.2007.06.015
Liu ZQ, Zhang XH, Xue YP, Xu M, Zheng YG (2014) Improvement of Alcaligenes faecalis nitrilase by gene site saturation mutagenesis and its application in stereospecific biosynthesis of (R)-(–)-mandelic acid. J Agric Food Chem 62(20):4685–4694. https://doi.org/10.1021/jf405683f
Ma BD, Yu HL, Pan J, Liu JY, Ju X, Xu JH (2013) A thermostable and organic-solvent tolerant esterase from Pseudomonas putida ECU1011: catalytic properties and performance in kinetic resolution of alpha-hydroxy acids. Bioresour Technol 133:354–360. https://doi.org/10.1016/j.biortech.2013.01.089
Martínková L, Křen V (2010) Biotransformations with nitrilases. Curr Opin Chem Biol 14(2):130–137. https://doi.org/10.1016/j.cbpa.2009.11.018
Martínková L, Rucká L, Nešvera J, Pátek M (2017) Recent advances and challenges in the heterologous production of microbial nitrilases for biocatalytic applications. World J Microbiol Biotechnol 33(1):8. https://doi.org/10.1007/s11274-016-2173-6
Ni K, Wang H, Zhao L, Zhang M, Zhang S, Ren Y, Wei D (2013) Efficient production of (R)-(–)-mandelic acid in biphasic system by immobilized recombinant E. coli. J Biotechnol 167(4):433–440. https://doi.org/10.1016/j.jbiotec.2013.07.024
Osprian I, Fechter MH, Griengl H (2003) Biocatalytic hydrolysis of cyanohydrins: an efficient approach to enantiopure α-hydroxy carboxylic acids. J Mol Catal B-Enzym 24-25:89–98. https://doi.org/10.1016/S1381-1177(03)00113-9
Petříčková A, Sosedov O, Baum S, Stolz A, Martínková L (2012) Influence of point mutations near the active site on the catalytic properties of fungal arylacetonitrilases from Aspergillus niger and Neurospora crassa. J Mol Catal B-Enzym 77:74–80. https://doi.org/10.1016/j.molcatb.2012.01.005
Pham XH, Kim JM, Chang SM, Kim IH, Kim WS (2009) Enantioseparation of D/L-mandelic acid with L-phenylalanine in diastereomeric crystallization. J Mol Catal B-Enzym 60(1–2):87–92. https://doi.org/10.1016/j.molcatb.2008.12.023
Robertson DE, Chaplin JA, DeSantis G, Podar M, Madden M, Chi E, Richardson T, Milan A, Miller M, Weiner DP, Wong K, McQuaid J, Farwell B, Preston LA, Tan X, Snead MA, Keller M, Mathur E, Kretz PL, Burk MJ, Short JM (2004) Exploring nitrilase sequence space for enantioselective catalysis. Appl Environ Microbiol 70(4):2429–2436. https://doi.org/10.1128/AEM.70.4.2429-2436.2004
Rucká L, Volkova O, Pavlík A, Kaplan O, Kracík M, Nešvera J, Martínková L, Pátek M (2014) Expression control of nitrile hydratase and amidase genes in Rhodococcus erythropolis and substrate specificities of the enzymes. Antonie Van Leeuwenhoek 105(6):1179–1190. https://doi.org/10.1007/s10482-014-0179-3
Rustler S, Motejadded H, Altenbuchner J, Stolz A (2008) Simultaneous expression of an arylacetonitrilase from Pseudomonas fluorescens and a (S)-oxynitrilase from Manihot esculenta in Pichia pastoris for the synthesis of (S)-mandelic acid. Appl Microbiol Biotechnol 80(1):87–97. https://doi.org/10.1007/s00253-008-1531-1
Saeed A, Shahzad D, Faisal M, Larik FA, El-Seedi HR, Channar PA (2017) Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel. Chirality 29(11):684–707. https://doi.org/10.1002/chir.22742
Shangguan JJ, Fan LQ, Ju X, Zhu QQ, Wang FJ, Zhao J, Xu JH (2012) Expression and characterization of a novel enantioselective lipase from Aspergillus fumigatus. Appl Biochem Biotechnol 168(7):1820–1833. https://doi.org/10.1007/s12010-012-9899-x
Sosedov O, Matzer K, Bürger S, Kiziak C, Baum S, Altenbuchner J, Chmura A, van Rantwijk F, Stolz A (2009) Construction of recombinant Escherichia coli catalysts which simultaneously express an (S)-oxynitrilase and different nitrilase variants for the synthesis of (S)-mandelic acid and (S)-mandelic amide from benzaldehyde and cyanide. Adv Synth Catal 351(10):1531–1538. https://doi.org/10.1002/adsc.200900087
Sosedov O, Baum S, Bürger S, Matzer K, Kiziak C, Stolz A (2010) Construction and application of variants of the Pseudomonas fluorescens EBC191 arylacetonitrilase for increased production of acids or amides. Appl Environ Microbiol 76(11):3668–3674. https://doi.org/10.1128/AEM.00341-10
Sosedov O, Stolz A (2014) Random mutagenesis of the arylacetonitrilase from Pseudomonas fluorescens EBC191 and identification of variants, which form increased amounts of mandeloamide from mandelonitrile. Appl Microbiol Biotechnol 98(4):1595–1607. https://doi.org/10.1007/s00253-013-4968-9
Sun HH, Wang HL, Gao WY, Chen LF, Wu K, Wei DZ (2015) Directed evolution of nitrilase PpL19 from Pseudomonas psychrotolerans L19 and identification of enantiocomplementary mutants toward mandelonitrile. Biochem Biophys Res Commun 468(4):820–825. https://doi.org/10.1016/j.bbrc.2015.11.038
Thuku RN, Brady D, Benedik MJ, Sewell BT (2009) Microbial nitrilases: versatile, spiral forming, industrial enzymes. J Appl Microbiol 106(3):703–727. https://doi.org/10.1111/j.1365-2672.2008.03941.x
Veselá AB, Křenková A, Martínková L (2015) Exploring the potential of fungal arylacetonitrilases in mandelic acid synthesis. Mol Biotechnol 57(5):466–474. https://doi.org/10.1007/s12033-015-9840-y
Veselá AB, Rucká L, Kaplan O, Pelantová H, Nešvera J, Pátek M, Martínková L (2016) Bringing nitrilase sequences from databases to life: the search for novel substrate specificities with a focus on dinitriles. Appl Microbiol Biotechnol 100(5):2193–2202. https://doi.org/10.1007/s00253-015-7023-1
Wang HL, Sun HH, Wei DZ (2013a) Discovery and characterization of a highly efficient enantioselective mandelonitrile hydrolase from Burkholderia cenocepacia J2315 by phylogeny-based enzymatic substrate specificity prediction. BMC Biotechnol 13:14. https://doi.org/10.1186/1472-6750-13-14
Wang P, Yang JF, Jiang L, Feng J, Yang CL, Li DL (2013b) A bi-enzymatic system for efficient enantioselective bioconversion of racemic mandelic acid. J Mol Catal B-Enzym 94:47–50. https://doi.org/10.1016/j.molcatb.2013.05.009
Wang HL, Fan HY, Sun HH, Zhao L, Wei DZ (2015a) Process development for the production of (R)-(−)-mandelic acid by recombinant Escherichia coli cells harboring nitrilase from Burkholderia cenocepacia J2315. Org Process Res Dev 19(12):2012–2016. https://doi.org/10.1021/acs.oprd.5b00269
Wang HL, Gao WY, Sun HH, Chen LF, Zhang L, Wang XD, Wei DZ (2015b) Protein engineering of a nitrilase from Burkholderia cenocepacia J2315 for efficient and enantioselective production of (R)-o-chloromandelic acid. Appl Environ Microbiol 81(24):8469–8477. https://doi.org/10.1128/AEM.02688-15
Wang P, Li DL Yang JF, Jiang L, Feng J, Yang CL, Shi RF (2014) Immobilization of (S)-mandelate dehydrogenase and its catalytic performance on stereoselective transformation of mandelic acid. J Taiwan Inst Chem Eng 45(3):744–748. https://doi.org/10.1016/j.jtice.2013.09.016
Xiao MT, Huang YY, Shi XA, Guo YH (2005) Bioreduction of phenylglyoxylic acid to R-(–)-mandelic acid by Saccharomyces cerevisiae FD11b. Enzym Microb Technol 37(6):589–596. https://doi.org/10.1016/j.enzmictec.2005.02.018
Xiao MT, Huang YY, Ye J, Guo YH (2008) Study on the kinetic characteristics of the asymmetric production of R-(–)-mandelic acid with immobilized Saccharomyces cerevisiae FD11b. Biochem Eng J 39(2):311–318. https://doi.org/10.1016/j.bej.2007.10.002
Xue YP, Xu M, Chen HS, Liu ZQ, Wang YJ, Zheng YG (2013a) A novel integrated bioprocess for efficient production of (R)-(–)-mandelic acid with immobilized Alcaligenes faecalis ZJUTB10. Org Process Res Dev 17(2):213–220. https://doi.org/10.1021/op3001993
Xue YP, Tian FF, Ruan LT, Liu ZQ, Zheng YG, Shen YC (2013b) Concurrent obtaining of aromatic (R)-2-hydroxyacids and aromatic 2-ketoacids by asymmetric oxidation with a newly isolated Pseudomonas aeruginosa ZJB1125. J Biotechnol 167(3):271–278. https://doi.org/10.1016/j.jbiotec.2013.06.015
Yamamoto K, Oishi K, Fujimatsu I, Komatsu KI (1991) Production of R-(–)-mandelic acid from mandelonitrile by Alcaligenes faecalis ATCC 8750. Appl Environ Microbiol 57(10):3028–3032
Yan PC, Xie JH, Zhang XD, Chen K, Li YQ, Zhou QL, Che DQ (2014) Direct asymmetric hydrogenation of α-keto acids by using the highly efficient chiral spiro iridium catalysts. Chem Commun 50(100):15987–15990. https://doi.org/10.1039/c4cc07643e
Yao CJ, Cao Y, Wu SS, Li S, He BF (2013) An organic solvent and thermally stable lipase from Burkholderia ambifaria YCJ01: purification, characteristics and application for chiral resolution of mandelic acid. J Mol Catal B-Enzym 85-86:105–110. https://doi.org/10.1016/j.molcatb.2012.08.016
Yildirim D, Tükel SS (2014) Asymmetric ammonolysis of (R/S)-mandelic acid by immobilized lipases via direct amidation of mandelic acid in biphasic media. Biocatal Biotransform 32(5–6):251–258. https://doi.org/10.3109/10242422.2014.971120
Yilmaz E (2012) Enantioselective enzymatic hydrolysis of racemic drugs by encapsulation in sol-gel magnetic sporopollenin. Bioprocess Biosyst Eng 35(4):493–502. https://doi.org/10.1007/s00449-011-0622-z
Yutthalekha T, Warakulwit C, Limtrakul J, Kuhn A (2015) Enantioselective recognition of DOPA by mesoporous platinum imprinted with mandelic acid. Electroanalysis 27(9):2209–2213. https://doi.org/10.1002/elan.201500145
Yutthalekha T, Wattanakit C, Lapeyre V, Nokbin S, Warakulwit C, Limtrakul J, Kuhn A (2016) Asymmetric synthesis using chiral-encoded metal. Nat Commun 7:12678. https://doi.org/10.1038/ncomms12678
Zhang ZJ, Pan JA, Liu JF, Xu JH, He YC, Liu YY (2011) Significant enhancement of (R)-mandelic acid production by relieving substrate inhibition of recombinant nitrilase in toluene–water biphasic system. J Biotechnol 152(1–2):24–29. https://doi.org/10.1016/j.jbiotec.2011.01.013
Zhang CS, Zhang ZJ, Li CX, Yu HL, Zheng GW, Xu JH (2012) Efficient production of (R)-o-chloromandelic acid by deracemization of o-chloromandelonitrile with a new nitrilase mined from Labrenzia aggregata. Appl Microbiol Biotechnol 5(1):91–99. https://doi.org/10.1007/s00253-012-3993-4
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The financial support by the Czech Science Foundation (project 18-00184S) and Czech Ministry of Education (LTC17009) are gratefully acknowledged.
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Martínková, L., Křen, V. Biocatalytic production of mandelic acid and analogues: a review and comparison with chemical processes. Appl Microbiol Biotechnol 102, 3893–3900 (2018). https://doi.org/10.1007/s00253-018-8894-8
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DOI: https://doi.org/10.1007/s00253-018-8894-8