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Advances in biotechnological production of β-alanine

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Abstract

β-Alanine (3-aminopropionic acid) is the only naturally occurring β-type amino acid. Although it is not incorporated into proteins, it has important physiological functions in the metabolism of animals, plants and microorganisms. Furthermore, it has attracted great interest due to its wide usage as a precursor of many significant industrial chemicals for medicine, feed, food, environmental applications and other fields. With the depletion of fossil fuels and concerns regarding environmental issues, biological production of β-alanine has attracted more attention relative to chemical methods. In this review, we first summarize the pathways through which natural microorganisms synthesize β-alanine. Then, the current research progress in the biological synthesis of β-alanine is also elaborated. Finally, we discuss the main problems and challenges in optimizing the biological pathways, offering perspectives on promising new biological approaches.

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Not applicable (as the work did not involve or use any novel microbial strain, plasmid, virus, other material such as prions or cell lines and nucleotide or amino acid sequence data).

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Not applicable (as the work did not involve software application or custom code).

References

  • Andersen SO (1979) Biochemistry of insect cuticle. Annu Rev Entomol 24:29–61

    Google Scholar 

  • Campbell LL (1957) Reductive degradation of pyrimidines. J Biol Chem 227:693–700

    Google Scholar 

  • Chen M, Qi Y, Xiao Y, Hua C, Li J, Liang A (2018) Biocatalytic synthesis of β-alanine from fumaric acid by a two-enzyme system bulletin of fermentation. Sci Technol 47:231–235

    Google Scholar 

  • Chen X, Lli Y, Gu Z, Ding Z, Zhang L, Shi G (2017) Expression and characterization of two L-aspartate alpha-decarboxylases. Microbiol China 44:2337–2344. https://doi.org/10.13344/j.microbiol.china.170009

    Google Scholar 

  • Cronan JE (1980) β-Alanine synthesis in Escherichia coli. J Bacteriol:1291–1297

  • Deng S, Zhang J, Cai Z, Li Y (2015) Characterization of L-aspartate-α-decarboxylase from Bacillus subtilis. Chin J Biotechnol 31(8):1184–1193

    Google Scholar 

  • Drakeford DR, Mukherjee I, Reid DM (1985) Some early responses of Helianthus annuus L. to flooding. J Exp Bot 36:1705–1715

    Google Scholar 

  • Fan X, Feng Z, Fang M, Zhang J, Chen G, Li L (2018) Heterologous expression of the Bacillus tequilensis L-aspartate α-decarboxylase in Escherichia coli and its high cell density fermentation. Food Science 39:144–150. https://doi.org/10.7506/spkx1002-6630-201802023

    Google Scholar 

  • Feng Z, Zhang J, Chen G, Ge Y, Zhang X, Zhu H (2019) Extracellular expression of L-aspartatealpha-decarboxylase from Bacillus tequilensis and its application in the biosynthesis of beta-alanine Appl Biochem Biotechnol 189:273–283. https://doi.org/10.1007/s12010-019-03013-1

  • Galston AW, Sawhney RK (1990) Polyamines in plant physiology. Plant Physiol 94:406–410

    Google Scholar 

  • Gao L, Qiu J (2007) Research advances in L-aspartate decarboxylase. Ind Microbiol 37:54–59

    Google Scholar 

  • Gao Y, Liu Z, Liu K, Zhou Z, Cui W (2017) Biocatalytic access to β-alanine by a two-enzyme cascade synthesis. Chin J Biotechnol 33:875–879

    Google Scholar 

  • Han C, Yao PY, Yuan J, Duan YT, Feng JH, Wang M, Wu QQ, Zhu DM (2015) Nitrilase-catalyzed hydrolysis of 3-aminopropionitrile at high concentration with a tandem reaction strategy for shifting the reaction to beta-alanine formation. J Mol Catal B Enzym 115:113–118. https://doi.org/10.1016/j.molcatb.2015.02.007

    Google Scholar 

  • Hayaishi O, Nishizuka Y, Tatibana M, Takeshita M, Kuno S (1961) Enzymatic studies on the metabolism of β-alanine. J Biol Chem 236:781–790

    Google Scholar 

  • He Y (2017) Research progress of biosynthesis of glutathione and its purification conditions Chem Intermed:79–80

  • Hilton MG, Mead GC, Elsden SR (1975) The metabolism of pyrimidines by proteolytic clostridia. Arch Microbiol 102:145–149

    Google Scholar 

  • Lee JW, Na D, Park JM, Lee J, Choi S, Lee SY (2012) Systems metabolic engineering of microorganisms for natural and non-natural chemicals. Nat Chem Biol 8:536–546. https://doi.org/10.1038/nchembio.970

    Google Scholar 

  • Li H, Lu X, Chen K, Yang J, Zhang A, Wang X, Ouyang P (2018) β-alanine production using whole-cell biocatalysts in recombinant Escherichia coli. Mol Catal 449:93–98. https://doi.org/10.1016/j.mcat.2018.02.008

    Google Scholar 

  • Li B, Su C, Chao F, Hong H, Zhang C (2019) Construction and optimization of high-yield β-alanine genetically engineered bacteria. J Dalian Polytech Univ 38:1–4

    Google Scholar 

  • Liang L, Jin S, Xu J, Zheng Y, Shen Y (2008) Isolation and identification of a bacterial strain G20 capable of β-aminopropionitrile bioconversion to β-alanine. Food Ferment Ind 34:485–488. https://doi.org/10.1210/jcem-66-3-485

    Google Scholar 

  • Liang S, Zhou L, Zhang B, Zhou Z (2017) Metabolic engineering of Escherichia coli for the production of β-alanine. Food Ferment Ind 43:13–18

    Google Scholar 

  • Liao HH, Gokarn RR, Gort JS, Jessen JH, Selifonova O (2010) Alanine 2,3-aminomutase. US7655451(B2)

  • Lin L (1999) The isolation, purification and properties of high activity aspartase. Acta Sci Nat Univ Jilinnensis 2(4):75–78

    Google Scholar 

  • Lundgren S, Gojkovic Z, Piskur J, Dobritzsch D (2003) Yeast beta-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases. J Biol Chem 278:51851–51862. https://doi.org/10.1074/jbc.M308674200

    Google Scholar 

  • Luo J, Xue J, Shen Y (2005) Synthesis and application of β-alanine. Amino Acids Biot Res 27:52–55

    Google Scholar 

  • Nozaki S, Webb ME, Niki H (2012) An activator for pyruvoyl-dependent l-aspartate α-decarboxylase is conserved in a small group of the γ-proteobacteria including Escherichia coli. Microbiol Open 1(3):298–310

    Google Scholar 

  • Painelli VdS, Nemezio KM, Pinto AJ, Franchi M, Andrade I, Riani LA, Saunders B, Sale C, Harris RC, Gualano B, Artioli GG (2018) High-intensity interval training augments muscle carnosine in the absence of dietary beta-alanine intake. Med Sci Sports Exerc 50:2242–2252. https://doi.org/10.1249/MSS.0000000000001697

    Google Scholar 

  • Parthasarathy A, Savka MA, Hudson AO (2019) The synthesis and role of β-alanine in plants Front. Plant Sci 10:921. https://doi.org/10.3389/fpls.2019.00921

    Google Scholar 

  • Pei W, Zhang J, Deng S, Tigu F, Li Y, Li Q, Cai Z, Li Y (2017) Molecular engineering of L-aspartate-alpha-decarboxylase for improved activity and catalytic stability. Appl Microbiol Biotechnol 101:6015–6021. https://doi.org/10.1007/s00253-017-8337-y

    Google Scholar 

  • Piao X, Wang L, Lin B, Chen H, Liu W, Tao Y (2019) Metabolic engineering of Escherichia coli for production of L-aspartate and its derivative beta-alanine with high stoichiometric yield. Metab Eng 54:244–254. https://doi.org/10.1016/j.ymben.2019.04.012

    Google Scholar 

  • Qi B, Wu S, Wang J, Qi G, Zhang H (2016) Physiological function and its application in animal feeding of β-Alanine. Chin J Anim Nutr 28:1027–1034

    Google Scholar 

  • Qian Y, Liu J, Song W, Chen X, Luo Q, Liu L (2018) Production of β-alanine from fumaric acid using a dual-enzyme cascade. ChemCatChem 10:4984–4991. https://doi.org/10.1002/cctc.201801050

    Google Scholar 

  • Qin M, You-Ran L, Gui-Yang S (2018) Advances in molecular mechanism and modification of bacterial L-aspartate alpha-decarboxylase. Microbiol China 45:1546–1554. https://doi.org/10.13344/j.microbiol.china.170835

    Google Scholar 

  • Ramjee MK, Genschel U, Abell C, Smith AG (1997) Escherichia coli L-aspartate-a-decarboxylase:preprotein processing and observation of reaction intermediates by electrospray mass spectrometry. Biochem J 323:661–669

    Google Scholar 

  • Rastogi R, Davies PJ (1989) Polyamine metabolism in ripening tomato. Plant Physiol 94:1449–1455

    Google Scholar 

  • Richardson G, Ding H, Rocheleau T, Mayhew G, Reddy E, Han Q, Christensen BM, Li J (2010) An examination of aspartate decarboxylase and glutamate decarboxylase activity in mosquitoes. Mol Biol Rep 37:3199–3205. https://doi.org/10.1007/s11033-009-9902-y

    Google Scholar 

  • Ross R, Monroe R (1972) β-Alanine metabolism in the housefly, musca domestica: concentrations in the larvae, pure, and adults. J Insect Physiol 18:791–796

    Google Scholar 

  • Schmitzberger F, Kilkenny ML, Lobley CMC, Webb ME, Vinkovic M, Vinkovic DM, Witty M, Chirgadze DY, Smith AG, Abell C, Blundell TL (2003) Structure constraints on protein self-processing in L-aspartate-α-decarboxylase. EMBO J 22:6193–6204

    Google Scholar 

  • Shen Y, Zhao L, Li Y, Zhang L, Shi G (2014) Synthesis of β-alanine from L-aspartate using L-aspartate-α-decarboxylase from Corynebacterium glutamicum. Biotechnol Lett 36:1681–1686. https://doi.org/10.1007/s10529-014-1527-0

    Google Scholar 

  • Song CW, Kim DI, Choi S, Jang JW, Lee SY (2013) Metabolic engineering of Escherichia coli for the production of fumaric acid. Biotechnol Bioeng 110:2025–2034. https://doi.org/10.1002/bit.24868

    Google Scholar 

  • Song CW, Lee J, Ko YS, Lee SY (2015) Metabolic engineering of Escherichia coli for the production of 3-aminopropionic acid. Metab Eng 30:121–129. https://doi.org/10.1016/j.ymben.2015.05.005

    Google Scholar 

  • Stegen S, Bex T, Vervaet C, Vanhee L, Achten E, Derave W (2014) β-Alanine dose for maintaining moderately elevated muscle carnosine levels. Med Sci Sports Exerc 46:1426–1432. https://doi.org/10.1249/MSS.0000000000000248

    Google Scholar 

  • Terano S, Suzuki Y (1978) Formation of β-alanine from spermine and spermine in maize shoots. Phytochemistry 17:148–149

    Google Scholar 

  • Tigu F, Zhang J, Liu G, Cai Z, Li Y (2018) A highly active pantothenate synthetase from Corynebacterium glutamicum enables the production of D-pantothenic acid with high productivity. Appl Microbiol Biotechnol 102:6039–6046. https://doi.org/10.1007/s00253-018-9017-2

    Google Scholar 

  • Tomita H, Yokooji Y, Ishibashi T, Imanaka T, Atomi H (2014) An archaeal glutamate decarboxylase homolog functions as an aspartate decarboxylase and is involved in beta-alanine and coenzyme A biosynthesis. J Bacteriol 196:1222–1230. https://doi.org/10.1128/JB.01327-13

    Google Scholar 

  • Wang C, Ye W, Xue L, Liu Z, Zhou Z (2019) Modification of aspartate α-decarboxylase from Tribolium castaneum and its application in producing β-alanine. Food Ferment Ind 45:7–13

    Google Scholar 

  • Wasternack C (1978) Degradation of pyrimidines—enzymes, localization and role in metabolism. Biochem Physiol Pflanzen 173:467–499. https://doi.org/10.1016/s0015-3796(17)30527-9

    Google Scholar 

  • West TP, Chu C-p (1985) Growth of Pseudomonas chlororaphis on pyrimidines and pyrimidine analogues. Microbios Letters 30:73–77

    Google Scholar 

  • White WH, Gunyuzlu PL, Toyn JH (2001) Saccharomyces cerevisiae is capable of de novo pantothenic acid biosynthesis involving a novel pathway of β-alanine production from spermine. J Biol Chem 276:10794–10800. https://doi.org/10.1074/jbc.M009804200

    Google Scholar 

  • White WH, Skatrud PL, Xue Z, Toyn JH (2002) Specialization of function among aldehyde dehydrogenases:the ALD2 and ALD3 genes are required for β-Alanine biosynthesis in Saccharomyces cerevisiae. Genet Soc Am 163:69–77

    Google Scholar 

  • Williamson JM, Brown GM (1979) Purification and properties of L-Aspartate-alpha-decarboxylase, an enzyme that catalyzes the formation of beta-alanine in Escherichia coli. Biol Chem 254:8074–8082

    Google Scholar 

  • Ye W, Xue L, Wang C, Cui W, Zhou Z, Liu Z (2019) Characterization of enzymatic properties of an insect-derived L-aspartate-α-decarboxylase variant. Food Ferment Ind 45:63–67

    Google Scholar 

  • Zhang K, Lu N, Xu H (1996) Reaction kinetics and process simulation for producing β-alanine by acrylic acid ammoniation (I): Kinetics of the reaction of acrylic acid with aqueous ammonia. Chem React Eng Technol 12:160

    Google Scholar 

  • Zhang T, Zhang R, Xu M, Zhang X, Yang T, Liu F, Yang S, Rao Z (2018) Glu56Ser mutation improves the enzymatic activity and catalytic stability of Bacillus subtilis L-aspartate alpha-decarboxylase for an efficient β-alanine production. Process Biochem 70:117–123. https://doi.org/10.1016/j.procbio.2018.04.004

    Google Scholar 

  • Zhao L, Zhang L, Shi G (2013) Expression of L-aspartate α-decarboxylase from Corynebacterium glutamicum in Escherichia coli and its application in enzymatic synthesis of β-alanine. Microbiol China 1:605

    Google Scholar 

  • Zou X, Guo L, Huang L, Li M, Zhang S, Yang A, Zhang Y, Zhu L, Zhang H, Zhang J, Feng Z (2020) Pathway construction and metabolic engineering for fermentative production of beta-alanine in Escherichia coli. Appl Microbiol Biotechnol. https://doi.org/10.1007/s00253-020-10359-8

    Google Scholar 

  • Zrenner R, Riegler H, Marquard CR, Lange PR, Geserick C, Bartosz CE (2009) Chen3 CT, Slocum RD A functional analysis of the pyrimidine catabolic pathway in Arabidopsis. New Phytol 183:117–132. https://doi.org/10.1111/j.1469-8137.2009.02843.x

    Google Scholar 

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Acknowledgements

The work was supported by the National Natural Science Foundation of China (NSFC-21621004 and NSFC-21776208).

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Authors and Affiliations

  1. Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Department of Biochemical Engineering, School of Chemical Engineering and Technology, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, People’s Republic of China

    Leilei Wang, Zhiwen Wang & Tao Chen

  2. Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People’s Republic of China

    Yufeng Mao & Hongwu Ma

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  1. Leilei Wang
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  2. Yufeng Mao
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  3. Zhiwen Wang
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  4. Hongwu Ma
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  5. Tao Chen
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All authors contributed to the study conception and design. Data collection and analysis were performed by Leilei Wang and Tao Chen. The first draft of the manuscript was written by Leilei Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hongwu Ma or Tao Chen.

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Wang, L., Mao, Y., Wang, Z. et al. Advances in biotechnological production of β-alanine. World J Microbiol Biotechnol 37, 79 (2021). https://doi.org/10.1007/s11274-021-03042-1

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