Abstract
Cadaverine, 1,5-diaminopentane, is one of the most promising chemicals for biobased-polyamide production and it has been successfully produced up to molar concentration. Pyridoxal 5′-phosphate (PLP) is a critical cofactor for inducible lysine decarboxylase (CadA) and is required up to micromolar concentration level. Previously the regeneration of PLP in cadaverine bioconversion has been studied and salvage pathway pyridoxal kinase (PdxY) was successfully introduced; however, this system also required a continuous supply of adenosine 5′-triphosphate (ATP) for PLP regeneration from pyridoxal (PL) which add in cost. Herein, to improve the process further a method of ATP regeneration was established by applying baker’s yeast with jhAY strain harboring CadA and PdxY, and demonstrated that providing a moderate amount of adenosine 5′-triphosphate (ATP) with the simple addition of baker’s yeast could increase cadaverine production dramatically. After optimization of reaction conditions, such as PL, adenosine 5′-diphosphate, MgCl2, and phosphate buffer, we able to achieve high production (1740 mM, 87% yield) from 2 M l-lysine. Moreover, this approach could give averaged 80.4% of cadaverine yield after three times reactions with baker’s yeast and jhAY strain. It is expected that baker’s yeast could be applied to other reactions requiring an ATP regeneration system.
This is a preview of subscription content, access via your institution.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.





References
- 1.
Han Y-H, Park Y-L, Yang S-Y, Jung H-R, Joo JC, Song B-K, Lee SH, Park K, Ahn J-O, Yang Y-H (2020) Selective extraction of glutaric acid from biological production systems using n-butanol. J Ind Eng Chem 82:98–104
- 2.
Wei G, Zhang A, Lu X, He F, Li H, Xu S, Li G, Chen K, Ouyang P (2020) An environmentally friendly strategy for cadaverine bio-production: in situ utilization of CO2 self-released from l-lysine decarboxylation for pH control. J CO2 Util 37:278–284
- 3.
Xue C, Hsu K-M, Ting W-W, Huang S-F, Lin H-Y, Li S-F, Chang J-S, Ng I-S (2020) Efficient biotransformation of l-lysine into cadaverine by strengthening pyridoxal 5′-phosphate-dependent proteins in Escherichia coli with cold shock treatment. Biochem Eng J 107659.
- 4.
Shin J, Joo JC, Lee E, Hyun SM, Kim HJ, Park SJ, Yang Y-H, Park K (2018) Characterization of a whole-cell biotransformation using a constitutive lysine decarboxylase from Escherichia coli for the high-level production of cadaverine from industrial grade l-lysine. Appl Biochem Biotechnol 185:909–924
- 5.
Liu Y, Zheng Y, Wu H, Zhang W, Ren T, You S, Qi W, Su R, He Z (2020) Development of an integrated process for the production of high-purity cadaverine from lysine decarboxylase. J Chem Technol Biotechnol 95:1542–1549
- 6.
Bhatia SK, Bhatia RK, Yang Y-H (2016) Biosynthesis of polyesters and polyamide building blocks using microbial fermentation and biotransformation. Rev Environ Sci Bio Technol 15:639–663
- 7.
Kim J, Seo H-M, Bhatia SK, Song H-S, Kim J-H, Jeon J-M, Choi K-Y, Kim W, Yoon J-J, Kim Y-G (2017) Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli. Sci Rep 7:39768
- 8.
Kim J-H, Kim HJ, Kim YH, Jeon JM, Song HS, Kim J, No S-Y, Shin J-H, Choi K-Y, Park KM (2016) Functional study of lysine decarboxylases from Klebsiella pneumoniae in Escherichia coli and application of whole cell bioconversion for cadaverine production. J Microbiol Biotechnol 26:1586–1592
- 9.
Zhou N, Zhang A, Wei G, Yang S, Xu S, Chen K, Ouyang P (2020) Cadaverine production from l-lysine with chitin-binding protein-mediated lysine decarboxylase immobilization. Front Bioeng Biotechnol 8:103
- 10.
Bhatia SK, Yang Y-H (2017) Microbial production of volatile fatty acids: current status and future perspectives. Rev Environ Sci Bio Technol 16:327–345
- 11.
Bhatia SK, Joo H-S, Yang Y-H (2018) Biowaste-to-bioenergy using biological methods—a mini-review. Energy Convers Manag 177:640–660
- 12.
Rohles CM, Gläser L, Kohlstedt M, Gießelmann G, Pearson S, del Campo A, Becker J, Wittmann C (2018) A bio-based route to the carbon-5 chemical glutaric acid and to bionylon-6, 5 using metabolically engineered Corynebacterium glutamicum. Green Chem 20:4662–4674
- 13.
Hong YG, Moon YM, Choi TR, Jung HR, Yang SY, Ahn JO, Joo JC, Park K, Kim YG, Bhatia SK (2019) Enhanced production of glutaric acid by NADH oxidase and GabD-reinforced bioconversion from l-lysine. Biotechnol Bioeng 116:333–341
- 14.
Hong Y-G, Moon Y-M, Hong J-W, No S-Y, Choi T-R, Jung H-R, Yang S-Y, Bhatia SK, Ahn J-O, Park K-M (2018) Production of glutaric acid from 5-aminovaleric acid using Escherichia coli whole cell bio-catalyst overexpressing GabTD from Bacillus subtilis. Enzyme Microbial Technol 118:57–65
- 15.
Yang S-Y, Choi T-R, Jung H-R, Park Y-L, Han Y-H, Song H-S, Gurav R, Bhatia SK, Park K, Ahn J-O (2020) Development of glutaric acid production consortium system with α-ketoglutaric acid regeneration by glutamate oxidase in Escherichia coli. Enzyme Microb Technol 133:109446
- 16.
Yang S-Y, Choi T-R, Jung H-R, Park Y-L, Han Y-H, Song H-S, Bhatia SK, Park K, Ahn J-O, Jeon W-Y (2019) Production of glutaric acid from 5-aminovaleric acid by robust whole-cell immobilized with polyvinyl alcohol and polyethylene glycol. Enzyme Microb Technol 128:72–78
- 17.
Hui H, Bai Y, Fan T-P, Zheng X, Cai Y (2020) Biosynthesis of putrescine from l-arginine using engineered Escherichia coli whole cells. Catalysts 10:947
- 18.
Sun L, Gong M, Lv X, Huang Z, Gu Y, Li J, Du G, Liu L (2020) Current advance in biological production of short-chain organic acid. Appl Microbiol Biotechnol
- 19.
Kim HJ, Kim YH, Shin J-H, Bhatia SK, Sathiyanarayanan G, Seo H-M, Choi KY, Yang Y-H, Park K (2015) Optimization of direct lysine decarboxylase biotransformation for cadaverine production with whole-cell biocatalysts at high lysine concentration. J Microbiol Biotechnol 25:1108–1113
- 20.
Sagong H-Y, Kim K-J (2017) Lysine decarboxylase with an enhanced affinity for pyridoxal 5-phosphate by disulfide bond-mediated spatial reconstitution. PLoS ONE 12:e0170163
- 21.
Park SH, Soetyono F, Kim HK (2017) Cadaverine production by using cross-linked enzyme aggregate of Escherichia coli lysine decarboxylase. J Microbiol Biotechnol 27:289–296
- 22.
Rui J, You S, Zheng Y, Wang C, Gao Y, Zhang W, Qi W, Su R, He Z (2020) High-efficiency and low-cost production of cadaverine from a permeabilized-cell bioconversion by a Lysine-induced engineered Escherichia coli. Biores Technol 302:122844
- 23.
Kim HT, Baritugo K-A, Oh YH, Kang K-H, Jung YJ, Jang S, Song BK, Kim I-K, Lee MO, Hwang YT (2019) High-level conversion of l-lysine into cadaverine by Escherichia coli whole cell biocatalyst expressing Hafnia alveil-lysine decarboxylase. Polymers 11:1184
- 24.
Hong EY, Lee SG, Park BJ, Lee JM, Yun H, Kim BG (2017) Simultaneously enhancing the stability and catalytic activity of multimeric lysine decarboxylase CadA by engineering interface regions for enzymatic production of cadaverine at high concentration of lysine. Biotechnol J 12:1700278
- 25.
Qian ZG, Xia XX, Lee SY (2011) Metabolic engineering of Escherichia coli for the production of cadaverine: a five carbon diamine. Biotechnol Bioeng 108:93–103
- 26.
Moorthi YM, Yang SY, Choi TR, Jung HR, Song HS, Hoon Han Y, Park HY, Bhatia SK, Gurav R, Park K (2019) Enhanced production of cadaverine by the addition of hexadecyltrimethylammonium bromide to whole cell system with regeneration of pyridoxalphosphate and ATP. Enzyme Microb Technol 127:58–64
- 27.
Kim J-H, Kim J, Kim H-J, Sathiyanarayanan G, Bhatia SK, Song H-S, Choi Y-K, Kim Y-G, Park K, Yang Y-H (2017) Biotransformation of pyridoxal 5′-phosphate from pyridoxal by pyridoxal kinase (pdxY) to support cadaverine production in Escherichia coli. Enzyme Microb Technol 104:9–15
- 28.
Kim J, Seo H-M, Bhatia SK, Song H-S, Kim J-H, Jeon J-M, Choi K-Y, Kim W, Yoon J-J, Kim Y-G (2017) Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli. Sci Rep 7:1–9
- 29.
Leong YK, Chen C-H, Huang S-F, Lin H-Y, Li S-F, Ng I-S, Chang J-S (2020) High-level l-lsyine bioconversion into cadaverine with enhanced productivity using engineered Escherichia coli whole-cell biocatalyst. Biochem Eng J 107547
- 30.
Kwak DH, Lim HG, Yang J, Seo SW, Jung GY (2017) Synthetic redesign of Escherichia coli for cadaverine production from galactose. Biotechnol Biofuels 10:20
- 31.
Ma W, Cao W, Zhang B, Chen K, Liu Q, Li Y, Ouyang P (2015) Engineering a pyridoxal 5′-phosphate supply for cadaverine production by using Escherichia coli whole-cell biocatalysis. Sci Rep 5:1–10
- 32.
Yang S-Y, Han Y-H, Park Y-L, Park J-Y, No S-y, Jeong D, Park S, Park HY, Kim W, Seo S-O (2020) Production of L-theanine Using Escherichia coli WHOLE-CELL OVEREXPRESSING γ-glutamylmethylamide synthetase with baker’s yeast. J Microbiol Biotechnol 30:785–792
- 33.
Kameda A, Shiba T, Kawazoe Y, Satoh Y, Ihara Y, Munekata M, Ishige K, Noguchi T (2001) A novel ATP regeneration system using polyphosphate-AMP phosphotransferase and polyphosphate kinase. J Biosci Bioeng 91:557–563
- 34.
Yan B, Ding Q, Ou L, Zou Z (2014) Production of glucose-6-phosphate by glucokinase coupled with an ATP regeneration system. World J Microbiol Biotechnol 30:1123–1128
- 35.
Resnick SM, Zehnder AJ (2000) In vitro ATP regeneration from polyphosphate and AMP by polyphosphate: AMP phosphotransferase and adenylate kinase from Acinetobacter johnsonii 210A. Appl Environ Microbiol 66:2045–2051
- 36.
Wakisaka S, Ohshima Y, Ogawa M, Tochikura T, Tachiki T (1998) Characteristics and efficiency of glutamine production by coupling of a bacterial glutamine synthetase reaction with the alcoholic fermentation system of baker’s yeast. Appl Environ Microbiol 64:2952–2957
- 37.
Horinouchi N, Sakai T, Kawano T, Matsumoto S, Sasaki M, Hibi M, Shima J, Shimizu S, Ogawa J (2012) Construction of microbial platform for an energy-requiring bioprocess: practical 2′-deoxyribonucleoside production involving a C−C coupling reaction with high energy substrates. Microb Cell Fact 11:1–8
- 38.
Yamamoto S, Wakayama M, Tachiki T (2005) Theanine production by coupled fermentation with energy transfer employing Pseudomonas taetrolens Y-30 glutamine synthetase and baker’s yeast cells. Biosci Biotechnol Biochem 69:784–789
- 39.
Lin J-P, Tian J, You J-F, Jin Z-H, Xu Z-N, Cen P-L (2004) An effective strategy for the co-production of S-adenosyl-l-methionine and glutathione by fed-batch fermentation. Biochem Eng J 21:19–25
- 40.
Kim YH, Kim HJ, Shin J-H, Bhatia SK, Seo H-M, Kim Y-G, Lee YK, Yang Y-H, Park K (2015) Application of diethyl ethoxymethylenemalonate (DEEMM) derivatization for monitoring of lysine decarboxylase activity. J Mol Catal B Enzym 115:151–154
- 41.
Huang T-C, Chen M-H, Ho C-T (2002) Stability of biologically active pyridoxal and pyridoxal phosphate in the presence of lysine. J Am Chem Soc 143–154
- 42.
Yamamoto S, Wakayama M, Tachiki T (2008) Cloning and expression of Methylovorus mays no. 9 gene encoding γ-glutamylmethylamide synthetase: an enzyme usable in theanine formation by coupling with the alcoholic fermentation system of baker’s yeast. Biosci Biotechnol Biochem 72:101–109
Acknowledgements
This study was supported by the National Research Foundation of Korea (NRF) (NRF-2019R1F1A1058805 and NRF-2019M3E6A1103979), and the Research Program to solve the social issues of the NRF funded by the Ministry of Science and ICT (2017M3A9E4077234). This work was also supported by R&D Program of MOTIE/KEIT (20009508).
Author information
Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interest.
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
Han, YH., Kim, H.J., Choi, TR. et al. Improvement of cadaverine production in whole cell system with baker’s yeast for cofactor regeneration. Bioprocess Biosyst Eng (2021). https://doi.org/10.1007/s00449-020-02497-0
Received:
Accepted:
Published:
Keywords
- Bioproduction
- Cadaverine
- Pyridoxal 5′-phosphate
- Adenosine 5′-triphosphate
- Baker’s yeast