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Cadaverine
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING · 2015 ·Vol. 19 ·期 6 ·965-972 · IF 1.113

Cadaverine production by heterologous expression of Klebsiella oxytoca lysine decarboxylase

Li Naiqiang,Chou Howard,Yu Lijun,Xu Yan

Cadaverine, as a biogenic amine, is an important platform chemical for the production of industrial polymers, such as polyamides, polyurethanes, and nylon. Previous efforts focused on the bio-based production of cadaverine using two lysine decarboxylases of Escherichia coli CadA and LdcC. In this study, we report the biotransformation of cadaverine using a lysine decarboxylase from Klebsiella oxytoca . Codon optimization of the gene encoding this enzyme was carried on for the heterologous expression in E. coli , which led to a system that converted more than 24% lysine-HCl to cadaverine compared to the same system expressing CadA. The system was further optimized by using three different inducible promoters to control the expression of lysine decarboxylase gene of K. oxytoca in E. coli . The final optimized system converted lysine-HCl to cadaverine at a conversion rate of 0.133%/min/g. When the optimized system described above is coupled to an industrial process, the combined process has the potential to produce cadaverine with high conversion efficiency (46%) from sugar.

研究领域: 生物化学 · 合成生物学 · 工业微生物学
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BIOCHEMICAL ENGINEERING JOURNAL · 2025 · IF 3.8

Whole-cell catalytic synthesis of cadaverine by recombinant Corynebacterium glutamicum using corncob residue as carbohydrate feedstock

Ying-Ying Xu,Bin Zhang,Jie Bao

Industrial production of cadaverine primarily relies on whole-cell catalysis of lysine using engineered Escherichia coli as host cells. The growing interest in cadaverine as a monomer of biobased polyamides requires inexpensive, non-food carbohydrate feedstock for its bioproduction, rather than using food-derived sugars as feedstock. This study used corncob residue as the starting carbohydrate feedstock followed by enzymatic hydrolysis to obtain the sugars. Since E. coli was not tolerant to even minor inhibitor residues in corncob residue hydrolysate, the robust Corynebacterium glutamicum was used as the host bacterium followed by the metabolic modifications of secretory expression of lysine decarboxylase via Ncgl1289 and cgR_0949 , and cadaverine degradation pathway knockout. The final whole-cell catalysis of C. glutamicum recombinant using corncob hydrolysate as carbohydrate feedstock achieved a record-high 78.19   g/L of cadaverine with a conversion yield of 91%.

CAS / MDL: 54-47-7
研究领域: 工业微生物学 · 生物工程 · 代谢工程
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JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY · 2024 · IF 2.8

Separation of cadaverine from fermentation broths by salting-out

Huijie Zheng,Hansheng Liu,Xueqi Shi,Shuwen Liu,Weiyi Su,Hao Li

BACKGROUND Cadaverine is an important diamine to synthesize nylon. However, the lower product concentration in the cadaverine production makes the downstream separation more complex and costly, and has become a bottleneck for large-scale production. Therefore, in this study, the salting-out was used to efficiently separate cadaverine in the simulated fermentation broth. RESULTS After analyzing the pH of readily soluble potassium salts, three alkaline salting-out agents—K 3 PO 4 , K 2 CO 3 and K 4 P 2 O 7 —were utilized to perform the salting-out separation of cadaverine. The effects of the type and concentration of salting-out agents and cadaverine concentration on the distribution and selection behavior of cadaverine in the simulated fermentation broth were investigated. Particularly, when the concentration of cadaverine was 10 wt% and the K 3 PO 4 concentration was 500 g/kg, the recovery rate of cadaverine in the simulated fermentation broth with K 3 PO 4 salting-out agent was as high as 99.6%, which was significantly higher than that of other salting-out agents, and only 0.01 wt% cadaverine remained in the aqueous phase. CONCLUSION The salting-out ability of the three inorganic salts to cadaverine in the simulated fermentation broth was K 3 PO 4 >K 2 CO 3 >K 4 P 2 O 7 . Furthermore, within a certain range of cadaverine concentrations, the content of cadaverine in the aqueous phase and the amount of water residue in the organic phase could be calculated using a linear regression equation. Since inorganic salts have the advantages of good stability, low cost, non-toxicity and harmlessness, the salting-out process established in this study shows good potential for industrial application. © 2024 Society of Chemical Industry (SCI).

CAS / MDL: 462-94-2
研究领域: 生物化学 · 化工工程
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ENGINEERING IN LIFE SCIENCES · 2015 ·Vol. 16 ·期 3 ·299-305 · IF 2.485

Improved cadaverine production from mutant Klebsiella oxytoca lysine decarboxylase

Naiqiang Li,Howard Chou,Yan Xu

Cadaverine has the potential to become an important platform chemical for the production of nylon. Previously, a system that overexpresses the Klebsiella oxytoca lysine decarboxylase in Escherichia coli was engineered. The system was optimized by codon optimization, and tuning the expression level of the gene by testing various promoters and inducer concentrations. Here, we further improved the system by optimizing the sequence located in the region of the ribosome-binding site in order to enhance translation efficiency. We also identified mutant lysine decarboxylase enzymes that demonstrated enhanced cadaverine-production ability. Together, these modifications increased cadaverine production in the system by 50%, and the system has a yield of 80% from lysine-HCl under the conditions we tested. This is the first time that a system to produce cadaverine using the lysine decarboxylase from K. oxytoca performed at a level that is competitive with the traditional systems using the E. coli lysine decarboxylases in both lab-scale and batch fermentation conditions.

CAS / MDL: 657-27-2
研究领域: 生物技术 · 代谢工程 · 合成生物学
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BIOCHEMICAL ENGINEERING JOURNAL · 2021 · IF 3.978

Novel enzyme-metal-organic framework composite for efficient cadaverine production

Jiahao Yao,Zhuang Li,Xiuling Ji,Yaju Xue,Baozeng Ren,Hai Zhao,Yuhong Huang

Cadaverine is an important precursor for the synthesis of nylon 5X, which is used for engineering plastics and fibers. L -lysine can be converted to cadaverine by lysine decarboxylases with high catalytic activity and selectivity. However, the pH sensitivity and non-recyclability impede the practical application of lysine decarboxylases for cadaverine production. In this study, lysine decarboxylase (LdcEt) was immobilized on the surface of the zirconium-based metal-organic framework material (MOF) UIO-66-NH 2 via covalent linkage for the first time. Morphological and structural analysis of the enzyme-MOF composite ( [email protected] 2 ) indicated that LdcEt was successfully immobilized on the surface of UIO-66-NH 2 . Meanwhile, [email protected] 2 showed higher catalytic efficiency and enzyme activity , broader pH and temperature reaction range than free LdcEt. Compared with free enzymes , [email protected] 2 could catalyze more cadaverine in 2 h at high-level substrate concentration (365.3 g L −1 ). Furthermore, [email protected] 2 can also be reused for 10 cycles. These results proved that the efficient enzyme-MOF composite [email protected] 2 has great potential for the large scale cadaverine production.

研究领域: 生物技术 · 化学工程 · 材料科学
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ANALYTICAL SCIENCES · 2020 ·Vol. 37 ·期 2 ·267-274 · IF 2.049

Silver Nanoparticles for a Colorimetric Determination of Putrescine and Cadaverine in Biological Samples

Ghoto Saima Ameen,Khuhawar Muhammad Yar

A convenient and uncomplicated scheme has been projected for the quantitative determination of essential diamines putrescine (PUT) and cadaverine (CAD) via sodium dodecyl sulfate protected silver nanoparticles (SDS-AgNPs). This scheme is based on the chemical interaction of a SDS-AgNPs probe with PUT and CAD, leading to a color change from yellow to red or reddish brown. The interaction was investigated through different techniques such as using a UV-visible spectrophotometer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), dynamic light scattering spectroscopy (DLS) and the zeta potential. Both amines possess a close resemblance in structure (except for the addition of one more methylene group in CAD), and no any distinguishable color change was noted. However, the maximum absorption band at 580 and 600 nm was demonstrated for PUT and CAD correspondingly. The methodical response was observed at absorption ratios of 580/410 and 600/410 nm, with the linear regression within 4–12 and 6–14 μg/mL for PUT and CAD. The detection limits calculated for both the diamines PUT and CAD were 0.333 and 1.638 μg/mL. The scheme was successfully applied for determinations in biological samples, including spiked blood plasma and urine. Putrescine exhibited % recovery within 95.717–105.200%, while cadaverine was within 95.940–105.109%, respectively. The scheme was reproducible and precise with inter-day RSD ( n = 5) within 1.126, 0.018% and the intraday RSD ( n = 5) was within 0.005, 0.002% for PUT and CAD, respectively.

CAS / MDL: 333-93-7
研究领域: 分析化学 · 生物医学
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ACS Sustainable Chemistry & Engineering · 2021 · IF 8.198

Cellular Engineering and Biocatalysis Strategies toward Sustainable Cadaverine Production: State of the Art and Perspectives

Jiali Mi,Simin Liu,Haishan Qi,Jie Huang,Xiang Lan,Lei Zhang

Cadaverine, a diamine monomer, broadly exists in living organisms participating in metabolism processes. As a promising substitute of 1,6-diaminohexane, cadaverine can polymerize with dicarboxylic acids and yield biobased polyamides, polyamide (PA) 5×, showing ecofriendly and excellent mechanical properties in the fields of electronics, automobile, material, storage, and others. Due to the increasing attentions on environment problems, biopolyamide is expected to be an ideal and green material to substitute conventional chemistry polyamide. This review summarizes the properties, potential applications, and production strategies about cadaverine and mainly focuses on the recent developments by cellular engineering Escherichia coli and Corynebacterium glutamicum as main workhorses. In addition, the key enzyme lysine decarboxylase decorated by means of immobilization and mutation to efficiently catalyze lysine and its catalysis mechanisms are also discussed. In order to achieve industrial applications, the indispensable steps of separation and purification are described as well and perspectives for cadaverine manufacturing from renewable resources are further provided.

CAS / MDL: 462-94-2
研究领域: 生物化学 · 微生物学 · 合成生物学
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JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY · 2020 ·Vol. 95 ·期 5 ·1542-1549 · IF 2.75

Development of an integrated process for the production of high-purity cadaverine from lysine decarboxylase

Yuxuan Liu,Yunxin Zheng,Hao Wu,Wei Zhang,Tianyu Ren,Shengping You,Wei Qi,Rongxin Su,Zhimin He

BACKGROUND Cadaverine is a natural polyamine that can replace fossil-derived hexamethylene diamine to produce bio-based polyamide. Despite huge developments in cadaverine bioproduction, an econo"mically attractive purification process is a highly important part of the production of high-purity cadaverine. RESULTS This study utilized l -lysine hydrochloride as a substrate for the production of high-purity cadaverine via a litre-scale integrated process incorporating fermentation, bioproduction, deprotonation, extraction and rectification. First, 8.24 U mg –1 lysine decarboxylase activity and 205 g L –1 cadaverine with a yield of 91.61% were achieved through the fermentation of low-cost industrial culture by engineered Escherichia coli and the bioproduction of cadaverine by lysine decarboxylase. Secondly, four integrated purification methods – deprotonation-evaporation, pH adjustment-deprotonation-evaporation, deprotonation-extraction-evaporation and deprotonation-extraction-rectification – were explored, and the conditions of each unit operation in the chosen method (deprotonation-extraction-rectification) were optimized. Then the optimized method was applied to a 2-L purification system, resulting in 99% purity of cadaverine with a yield of 87.47%. Furthermore, the n -butanol recovery ratio reached 91.25%, effectively avoiding the waste of resources and environmental pollution, and thus reducing purification costs. CONCLUSION The proposed experimental approach proves that this integrated process leads to the production of high-purity cadaverine. In the 2-L-scale integrated process, 358.64 g cadaverine of 99% purity was produced at a cost of US$3.99 (US$1.11 per 100 g), which is far below its market price (US$784.71 per 100 g). This integrated process provides a potential way for the industrial-scale production of bio-based cadaverine. © 2020 Society of Chemical Industry

CAS / MDL: 605-65-2
研究领域: 生物工程 · 化学工业
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY · 2026 · IF 3.5

Characterization and Immobilization of a High Activity Lysine Decarboxylase from Serratia Proteamaculans NJ303 for Cadaverine Production

Wei Guoguang,Zhou Ning,Wei Jie,Zhang Alei,Chen Kequan,He Hao

Cadaverine, an essential precursor for bio-based nylon PA5X production, has emerged as a highly valuable compound in the engineered plastics and synthetic fibers industry. Current industrial biomanufacturing of cadaverine depends critically on the enzymatic activity of L-lysine decarboxylase (LDC). In this investigation, we systematically evaluated ten LDC variants originating from six distinct bacterial species, all cloned and expressed in Escherichia coli BL21(DE3). Comprehensive characterization identified Sp LDC from Serratia proteamaculans as the most promising candidate, demonstrating exceptional catalytic activity under alkaline conditions. Enzymatic analysis showed that Sp LDC established optimal activity at pH 6.5 and 52 °C, with remarkable stability maintained between pH 5.5-8.0 and temperatures of 37–52 °C during prolonged 12-hour incubations. Kinetic studies revealed favorable catalytic parameters ( K m = 11.5 mM, V max = 1000 U/mg), indicating efficient substrate conversion. To enhance industrial applicability, we developed an immobilized enzyme system by genetically fusing Sp LDC with a chitin-binding domain (ChBD) and subsequently immobilizing it on chitin supports. This engineered biocatalyst demonstrated superior performance compared to whole-cell systems, achieving a 3.4-fold enhancement in cadaverine production efficiency. The immobilized preparation exhibited excellent operational stability, retaining over 50% of its initial activity through ten repeated reaction cycles. This work establishes an efficient, stable, and reusable enzymatic platform for cadaverine biosynthesis, offering significant potential for sustainable nylon PA5X production at industrial scales.

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Bioresource Technology Reports · 2022 · IF 0

Cofactor self-sufficient by co-immobilization of pyridoxal 5′-phosphate and lysine decarboxylase for cadaverine production

Jiali Mi,Simin Liu,Yan Du,Haishan Qi,Lei Zhang

Cadaverine (1,5-diaminopentane) has widespread applications in industry, agriculture and medicine. Cadaverine can be biotransformed from l -lysine by lysine decarboxylasey which is a pyridoxal 5′-phosphate (PLP)-dependent enzyme. Herein, barium alginate microspheres were fabricated by electro-dripping and employed as immobilized metal ion affinity chromatography matrix to purify and immobilize engineered lysine decarboxylase CadA-EK. Besides, polyethyleneimine (PEI) was employed for co-immobilizing PLP and enzymes (cCadA-EK-PEI/PLP). The cCadA-EK-PEI/PLP can produced 184.53 g/L cadaverine with yield of 90.03% in 2 mol/L lysine solution. And the stability of co-immobilized CadA-EK was 1–4 times higher than that of iCadA-EK + PLP in environmental factors, and the catalytic efficiency k cat / K m was increased by 3.4-fold. Furthermore, a continuous flow microreactor with the co-immobilized enzymes and cofactors was developed to catalyze lysine, with 14.28 g/(L·h) productivity of cadaverine, which displayed great potential for cadaverine biosynthesis. This work provides alternative strategy for the one-step purification and co-immobilization of enzyme and cofactor.

研究领域: 生物催化 · 酶工程 · 生物合成 · 材料科学
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BIOCHEMICAL ENGINEERING JOURNAL · 2022 · IF 4.446

Enhancing pH stability of lysine decarboxylase via rational engineering and its application in cadaverine industrial production

Siyuan Gao,Alei Zhang,Ding Ma,Kun Zhang,Jing Wang,Xin Wang,Kequan Chen

Cadaverine, an important C5 platform compound, is the raw material of polyamides . Under a carbon neutral context, cadaverine bio-production using lysine decarboxylase as a catalyst from the sustainable resource L -lysine is more attractive than chemical synthesis from fossil resources because it is environmentally-friendly and highly efficient. However, the alkaline conditions caused by accumulation of cadaverine decreases lysine decarboxylase activity, which limits its industrial applications. Herein, we aimed to improve cadaverine enzymatic production via enhancing stability of lysine decarboxylase from Escherichia coli (EcCadA) under alkaline pH by rational engineering. Mutations of interfacial disulfide bonds between subunits in the EcCadA decamer, M1 (L89C/L442C), M2 (F102C/L547C), and M3 (V12C/D41C) were chosen. M3 exhibited a 6-fold increase in cadaverine production at pH 10.0. Non-reduced SDS-PAGE analysis demonstrated that the proportion of decamers was greatly increased compared to wild-type enzyme . In addition, molecular dynamics simulations showed that the distance between subunits increased with increased pH, especially in region B. Finally, the fed-batch bioconversion of cadaverine from L -lysine in a 5 L fermenter using M3 by whole-cell catalysis led to 418 g/L cadaverine, which is the highest titer produced to date. This study provided a more efficient enzyme to industrially produce cadaverine with reduced acid use.

CAS / MDL: 657-27-2
研究领域: 生物技术 · 酶工程 · 工业微生物学 · 分子生物学 · 化学工程
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Journal of Food Measurement and Characterization · 2021 ·Vol. 15 ·期 2 ·1747-1753 · IF 2.431

Colorimetric detection of putrescine and cadaverine in aquatic products based on the mimic enzyme of (Fe,Co) codoped carbon dots

Li Yi-Fang,Lin Zheng-Zhong,Hong Cheng-Yi,Huang Zhi-Yong

A facile colorimetric method for rapid detection of putrescine (Put) and cadaverine (Cad) based on the peroxidase-like activity of (Fe,Co) codoped-CDs was developed. With the enzymatic hydrolysis by diamine oxidase (EC 1.4.3.6, DAO), Biogenic amines (BAs) were decomposed to produce H 2 O 2 which oxidizes 3,3',5,5'-tetramethyl-benzidine with the catalysis of (Fe,Co)-codoped CDs. By means of principal component analysis, Put and Cad were differentiated from BAs and their total amounts were detected by measuring the spectral absorption at 652 nm with a linear range from 0.25 to 10 mg kg −1 . The colorimetric method was applied to the detection of Put and Cad in various fish samples with a detection limit ((3σ/k, n = 9)) of 0.06 mg kg −1 . Besides verifying with HPLC, the recoveries of the colorimetric method were also tested by spiking standards at three levels with the range of 98.2%–115.7%, indicating that the established colorimetric method was accurate and sensitive.

研究领域: 食品科学 · 生物化学 · 分析化学
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