Abstract
Mannitol is a naturally occurring six-carbon sugar alcohol that has wide applications in the food and pharmaceutical industry because of its many properties, namely being a natural sweetener with a low metabolism and no glycemic index. The increasing demand for mannitol has spurred many studies of its production. Compared with its chemical synthesis and extraction from plants, both of which are difficult to satisfy for industrial requirements, biotechnological production of mannitol has received considerably more attention and interest from scientists because of its known advantages over those two methods. Accordingly, in this review, we summarize recent advances made in the production of mannitol through various biotechnological methods. The physicochemical properties, sources, and physiological functionalities and applications of mannitol are systematically covered and presented. Then, different determination methods for mannitol are also described and compared. Furthermore, different biotechnological strategies for the production of mannitol via fermentation engineering, protein engineering, and metabolic engineering receive a detailed overview in terms of mannitol-producing strains, enzymes, and their key reaction parameters and conditions.
Key points
• Physiological functionalities and applications of mannitol are presented in detail.
• Different determination methods for mannitol are also described and compared.
• Various biotechnological strategies for the production of mannitol are reviewed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baumchen C, Bringer-Meyer S (2007) Expression of glfZ.m. increases D-mannitol formation in whole cell biotransformation with resting cells of Corynebacterium glutamicum. Appl Microbiol Biotechnol 76(3):545–552. https://doi.org/10.1007/s00253-007-0987-8
Baumchen C, Roth AH, Biedendieck R, Malten M, Follmann M, Sahm H, Bringer-Meyer S, Jahn D (2007) D-mannitol production by resting state whole cell biotransformation of D-fructose by heterologous mannitol and formate dehydrogenase gene expression in Bacillus megaterium. Biotechnol J 2(11):1408–1416. https://doi.org/10.1002/biot.200700055
Cao H, Yue M, Liu G, Du Y, Yin H (2018) Microbial production of mannitol by Lactobacillus brevis 3-A5 from concentrated extract of Jerusalem artichoke tubers. Biotechnol Appl Biochem 65(3):484–489. https://doi.org/10.1002/bab.1590
Carvalheiro F, Moniz P, Duarte LC, Esteves MP, Girio FM (2011) Mannitol production by lactic acid bacteria grown in supplemented carob syrup. J Ind Microbiol Biotechnol 38(1):221–227. https://doi.org/10.1007/s10295-010-0823-5
Chen G, Zhang L, Wu X, Ye J (2005) Determination of mannitol and three sugars in Ligustrum lucidum Ait. by capillary electrophoresis with electrochemical detection. Anal Chim Acta 530(1):15–21. https://doi.org/10.1016/j.aca.2004.08.053
Cheng H, Qian H, Cao Y (2008) Capillary electrophoresis - electrochemical detection of D-mannitol and sugars in Chrysanthemum. J Univ Sci Technol Suzhou (in Chinese) 25(3):46–50 http://www.cnki.com.cn/Article/CJFDTotal-TDSY200803014.htm
Dai Y, Meng Q, Mu W, Zhang T (2017) Recent advances in the applications and biotechnological production of mannitol. J Funct Foods 36:404–409. https://doi.org/10.1016/j.jff.2017.07.022
Du H, Ma X, Jiang M, Yan P, Zhao Y, Conrad Zhang Z (2020) Efficient Ni/SiO2 catalyst derived from nickel phyllosilicate for xylose hydrogenation to xylitol. Catal Today. https://doi.org/10.1016/j.cattod.2020.04.009
Fleming SC, Kapembwa MS, Laker MF, Levin GE, Griffin GE (1990) Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability. Clin Chem 36(5):797–799. https://doi.org/10.1093/clinchem/36.5.797
Fontes CP, Honorato TL, Rabelo MC, Rodrigues S (2009) Kinetic study of mannitol production using cashew apple juice as substrate. Bioprocess Biosyst Eng 32(4):493–499. https://doi.org/10.1007/s00449-008-0269-6
Gaspar P, Neves AR, Ramos A, Gasson MJ, Shearman CA, Santos H (2004) Engineering Lactococcus lactis for production of mannitol: high yields from food-grade strains deficient in lactate dehydrogenase and the mannitol transport system. Appl Environ Microbiol 70(3):1466–1474. https://doi.org/10.1128/aem.70.3.1466-1474.2004
Guicherd P, Peltier JP, Gout E, Bligny R, Marigo G (1997) Osmotic adjustment in Fraxinus excelsior L . : malate and mannitol accumulation in leaves under drought conditions. Trees 11(3):155–161. https://doi.org/10.1007/PL00009664
Ikawa T, Watanabe T, Nisizawa K (1972) Enzymes involved in the last steps of the biosynthesis of mannitol in brown algae. Plant Cell Physiol 13(6):1017–1029. https://doi.org/10.1093/oxfordjournals.pcp.a074808
Jiang H, Chen W, Zhao J, Zhang H (2005) Determination of mannitol in lactic acid bacteria fermentation system by spectrophotometry. Food Ferment Ind (in Chinese) 31(4):105–107. https://doi.org/10.13995/j.cnki.11-1802/ts.2005.04.028
Kaup B, Bringer-Meyer S, Sahm H (2005) D-Mannitol formation from D-glucose in a whole-cell biotransformation with recombinant Escherichia coli. Appl Microbiol Biotechnol 69(4):397–403. https://doi.org/10.1007/s00253-005-1996-0
Kiyoshima A, Kudo K, Hino Y, Ikeda N (2001) Sensitive and simple determination of mannitol in human brain tissues by gas chromatography–mass spectrometry. J Chromatogr B 758(1):103–108. https://doi.org/10.1016/S0378-4347(01)00145-1
Koko MYF, Hassanin HAM, Letsididi R, Zhang T, Mu W (2016) Characterization of a thermostable mannitol dehydrogenase from hyperthermophilic Thermotoga neapolitana DSM 4359 with potential application in mannitol production. J Mol Catal B Enzym 134:122–128. https://doi.org/10.1016/j.molcatb.2016.10.010
Kulbe KD, Schwab U, Gudernatsch W (1987) Enzyme-catalyzed production of mannitol and gluconic acid. Ann N Y Acad Sci 506(1):552–568. https://doi.org/10.1111/j.1749-6632.1987.tb23850.x
Li X, Bao T, Wang Y (1999) Determination of mannitol in Cordyceps sinensis by colorimetric method. Chin Herb Med (in Chinese) 30(1):19–21 http://www.cnki.com.cn/Article/CJFDTotal-ZCYO199901008.htm
Li H, Yang P, Chu D, Li H (2007) Selective maltose hydrogenation to maltitol on a ternary Co–P–B amorphous catalyst and the synergistic effects of alloying B and P. Appl Catal A Gen 325(1):34–40. https://doi.org/10.1016/j.apcata.2007.02.007
Liu H, Zhang S, Yu A, Qu L, Zhao Y, Huang H, Li J (2004) Studies on intestinal permeability of cirrhotic patients by analysis lactulose and mannitol in urine with HPLC/RID/MS. Bioorg Med Chem Lett 14(9):2339–2344. https://doi.org/10.1016/j.bmcl.2004.01.107
Livesey G (2003) Health potential of polyols as sugar replacers, with emphasis on low glycaemic properties. Nutr Res Rev 16(2):163–191. https://doi.org/10.1079/NRR200371
Lu F, Xu W, Wu H, Guang C, Zhang W, Mu W (2020) Purification and characterization of recombinant mannitol dehydrogenase from P. bacterium1109. Sci Technol Food Ind (in Chinese) http://kns.cnki.net/kcms/detail/11.1759.TS.20200403.0920.004.html
Madsen MA, Semerdzhiev S, Amtmann A, Tonon T (2018) Engineering mannitol biosynthesis in Escherichia coli and Synechococcus sp. PCC 7002 using a green algal fusion protein. ACS Synth Biol 7(12):2833–2840. https://doi.org/10.1021/acssynbio.8b00238
Meng Q, Zhang T, Wei W, Mu W, Miao M (2017) Production of mannitol from a high concentration of glucose by Candida parapsilosis SK26.001. Appl Biochem Biotechnol 181(1):391–406. https://doi.org/10.1007/s12010-016-2219-0
Mishra DK, Dabbawala AA, Truong CC, Alhassan SM, Jegal J, Hwang JS (2018) Ru–NiOx nanohybrids on TiO2 support prepared by impregnation-reduction method for efficient hydrogenation of lactose to lactitol. J Ind Eng Chem 68:325–334. https://doi.org/10.1016/j.jiec.2018.08.003
Mitchell H (2006) Sweeteners and sugar alternatives in food technology. Blackwell Publishing, Oxford
Neves AR, Ramos A, Shearman C, Gasson MJ, Santos H (2002) Catabolism of mannitol in Lactococcus lactis MG1363 and a mutant defective in lactate dehydrogenase. Microbiology 148(11):3467–3476. https://doi.org/10.1099/00221287-148-11-3467
Ortiz ME, Fornaguera MJ, Raya RR, Mozzi F (2012) Lactobacillus reuteri CRL 1101 highly produces mannitol from sugarcane molasses as carbon source. Appl Microbiol Biotechnol 95(4):991–999. https://doi.org/10.1007/s00253-012-3945-z
Parmentier S, Arnaut F, Soetaert W, Vandamme EJ (2005) Enzymatic production of D-mannitol with the Leuconostoc pseudomesenteroides mannitol dehydrogenase coupled to a coenzyme regeneration system. Biocatal Biotransfor 23(1):1–7. https://doi.org/10.1080/10242420500071664
Qianqian W (2010) Research progress in preparation and application of mannitol. Sci Technol Food Ind (in Chinese) 31(12):401–404. https://doi.org/10.13386/j.issn1002-0306.2010.12.009
Queneau Y, Chambert S, Besset C, Cheaib R (2008) Recent progress in the synthesis of carbohydrate-based amphiphilic materials: the examples of sucrose and isomaltulose. Carbohydr Res 343(12):1999–2009. https://doi.org/10.1016/j.carres.2008.02.008
Reshamwala SMS, Pagar SK, Velhal VS, Maranholakar VM, Talangkar VG, Lali AM (2014) Construction of an efficient Escherichia coli whole-cell biocatalyst for D-mannitol production. J Biosci Bioeng 118(6):628–631. https://doi.org/10.1016/j.jbiosc.2014.05.004
Rice T, Zannini E, Arendt EK, Coffey A (2019) A review of polyols– biotechnological production, food applications, regulation, labeling and health effects. Crit Rev Food Sci Nutr:1–18. https://doi.org/10.1080/10408398.2019.1625859
Rockwell K (2015) Therapeutic review: Mannitol. J Exo Pet Med 24(1):120–122. https://doi.org/10.1053/j.jepm.2014.11.002
Rzechonek DA, Dobrowolski A, Rymowicz W, Mirończuk AM (2018) Recent advances in biological production of erythritol. Crit Rev Biotechnol 38(4):620–633. https://doi.org/10.1080/07388551.2017.1380598
Saha BC (2006) Production of mannitol from inulin by simultaneous enzymatic saccharification and fermentation with Lactobacillus intermedius NRRL B-3693. Enzym Microb Technol 39(5):991–995. https://doi.org/10.1016/j.enzmictec.2006.02.001
Saha BC, Racine FM (2010) Effects of pH and corn steep liquor variability on mannitol production by Lactobacillus intermedius NRRL B-3693. Appl Microbiol Biotechnol 87(2):553–560. https://doi.org/10.1007/s00253-010-2552-0
Saha BC, Racine FM (2011) Biotechnological production of mannitol and its applications. Appl Microbiol Biotechnol 89(4):879–891. https://doi.org/10.1007/s00253-010-2979-3
Shawkat H, Westwood MM, Mortimer A (2012) Mannitol: a review of its clinical uses. Contin Edu Anaesth Crit Care Pain 12(2):82–85. https://doi.org/10.1093/bjaceaccp/mkr063
Singh H, Rai A, Yadav R, Sinha AK (2018) Glucose hydrogenation to sorbitol over unsupported mesoporous Ni/NiO catalyst. Mol Catal 451:186–191. https://doi.org/10.1016/j.mcat.2018.01.010
Soetaert W (1990) Production of mannitol with Leuconostoc mesenteroides. Mededelingen van de Faculteit Landbouwwetenschappen, Rijksuniversiteit Gent (Netherlands journal) 55(4):1549–1552 https://www.cabdirect.org/cabdirect/abstract/19920313622
Song SH, Vieille C (2009) Recent advances in the biological production of mannitol. Appl Microbiol Biotechnol 84(1):55–62. https://doi.org/10.1007/s00253-009-2086-5
Song SH, Ahluwalia N, Leduc Y, Delbaere LT, Vieille C (2008) Thermotoga maritima TM0298 is a highly thermostable mannitol dehydrogenase. Appl Microbiol Biotechnol 81(3):485–495. https://doi.org/10.1007/s00253-008-1633-9
Stoop JMH, Williamson JD, Mason Pharr D (1996) Mannitol metabolism in plants: a method for coping with stress. Trends Plant Sci 1(5):139–144. https://doi.org/10.1016/S1360-1385(96)80048-3
Takemura M, Iijima M, Tateno Y, Osada Y, Maruyama H (1978) Process for preparing D-mannitol. Google Patents https://patentimages.storage.googleapis.com/be/56/9f/548421a0cafc5c/US4083881.pdf
Tang Y, Liu Y, Zhang Y, Zhang J, Liu Y (1998) Hydrolytic hydrogenation of cane juice to product of mannitol and sorbitol. Sugarcane Canesugar (in Chinese) 2:41–44 http://www.cnki.com.cn/Article/CJFDTotal-GZTY199802011.htm
von Weymarn N, Hujanen M, Leisola M (2002) Production of D-mannitol by heterofermentative lactic acid bacteria. Process Biochem 37(11):1207–1213. https://doi.org/10.1016/S0032-9592(01)00339-9
Wang G, Zhao G, He D, Li J (2005) Preparation of crystalline mannitol by double isomerization. Food Res Develop (in Chinese) 26(4):82–84. https://doi.org/10.3969/j.issn.1002-1124.2005.03.022
Wei Q (2010) Research progress in preparation and application of mannitol. Sci Technol Food Ind (in Chinese) 31(12):401–404. https://doi.org/10.13386/j.issn1002-0306.2010.12.009
Xiang D, Wang X (2009) Research progress in the analysis and determination methods of mannitol. Sci Technol Food Ind (in Chinese) 30(12):420–423. https://doi.org/10.13386/j.issn1002-0306.2009.12.012
Xiao H, Wang Q, Bang-Berthelsen CH, Jensen PR, Solem C (2020) Harnessing adaptive evolution to achieve superior mannitol production by Lactococcus lactis using its native metabolism. J Agric Food Chem 68(17):4912–4921. https://doi.org/10.1021/acs.jafc.0c00532
Xie X, Zhang C, Zeng B (1998) Study on extraction method of mannitol in kelp. Appl Technol Market (in Chinese) 11:8–9 http://www.cnki.com.cn/Article/CJFDTotal-KJCK199811004.htm
Yoshikawa J, Habe H, Morita T, Fukuoka T, Imura T, Iwabuchi H, Uemura S, Tamura T, Kitamoto D (2014) Production of mannitol from raw glycerol by Candida azyma. J Biosci Bioeng 117(6):725–729. https://doi.org/10.1016/j.jbiosc.2013.11.016
Zhan T, Song J (2003) Progress in studies of mannitol in medicinal application. Chin J Mar Drugs 3:57–61 http://www.cnki.com.cn/Article/CJFDTotal-HYYW200303016.htm
Zhang M, Gu L, Cheng C, Ma J, Xin F, Liu J, Wu H, Jiang M (2018) Recent advances in microbial production of mannitol: utilization of low-cost substrates, strain development and regulation strategies. World J Microbiol Biotechnol 34(3):41. https://doi.org/10.1007/s11274-018-2425-8
Zhou W, Fan J (2005) Review of manufacturing mannitol. Sugarcane Canesugar (in Chinese) 5:46–50 http://www.cnki.com.cn/Article/CJFDTotal-GZTY200505011.htm
Funding
This work was supported by the National Natural Science Foundation of China (No. 31801583 and No. 31922073), the Natural Science Foundation of Jiangsu Province (No. BK20180607), and the National First-Class Discipline Program of Food Science and Technology of China (JUFSTR20180203).
Author information
Authors and Affiliations
Contributions
MC and HW wrote the paper. HW, WZ, and WM collected references and drew pictures. HW and CG designed the structure and discussed the manuscript. All the authors read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain studies with human participants or animals carried out by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Chen, M., Zhang, W., Wu, H. et al. Mannitol: physiological functionalities, determination methods, biotechnological production, and applications. Appl Microbiol Biotechnol 104, 6941–6951 (2020). https://doi.org/10.1007/s00253-020-10757-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-020-10757-y