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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2024, Vol. 44 Issue (4): 88-101    DOI: 10.13523/j.cb.2310023
综述     
维生素B6的生理活性与合成的研究进展*
周楚然,王美玲,黄建忠,柯崇榕**(),杨欣伟**()
福建师范大学生命科学学院 工业微生物发酵技术国家地方联合工程研究中心 工业微生物教育部工程中心 福州 350108
Advances in Physiological Activities and Synthesis of Vitamin B6
ZHOU Churan,WANG Meiling,HUANG Jianzhong,KE Chongrong**(),YANG Xinwei**()
Engineering Research Center of Industrial Microbiology, Ministry of Education, National and Local United, Engineering Research Center of Industrial Microbiology and Fermentation Technology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China
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摘要：

维生素B6(vitamin B6,VB6)属于水溶性维生素,由六种可相互转换的吡啶类化合物组成:吡哆醇(pyridoxine,PN)、吡哆醛(pyridoxal,PL)、吡哆胺(pyridoxamine,PM)、磷酸吡哆醛(pyridoxal 5'-phosphate,PLP)、磷酸吡哆醇(pyridoxine 5'-phosphate,PNP)和磷酸吡哆胺(pyridoxamine 5'-phosphate,PMP)。其中,PLP是VB6的生物活性形式,为180多种酶的辅因子。VB6具有抗炎、抗氧化、神经调节和抗肿瘤等多种生理功能,是重要的营养化学品。吡哆醇盐酸盐(PN·HCl)利用昂贵且有毒的化学物质通过噁唑法完全合成,是VB6目前最常见的商业形式。与化学合成相比,VB6的生物合成在无毒性、高纯度和可持续性等方面具有显著优势。目前利用微生物细胞工厂高水平生产VB6的尝试还处于起步阶段,随着对VB6生物合成的代谢途径、关键酶和稳态调控的深入研究,生物合成的VB6产量将会逐步提高,有望从根本上取代化学合成。对VB6的生理功能、化学合成和生物合成进行总结,重点介绍生物合成中涉及的代谢途径与稳态调控,提出开发VB6高产菌株的相关策略,以期为VB6的高效生物合成提供参考。
关键词： 维生素B6;  磷酸吡哆醛;  化学合成;  生物合成;  稳态调控    
Abstract:

Vitamin B6 (VB6) is a water-soluble vitamin, composed of six transformable pyridine compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP). PLP is the bioactive form of VB6, and is the cofactor of over 180 enzymes. VB6 is an important dietary chemical with several physiological functions such as anti-inflammatory, antioxidant, neuromodulatory, and anti-tumor. Pyridoxine hydrochloride is currently the most common commercial form of VB6, which is fully synthesized using expensive and toxic chemicals via the oxazole method. Compared with chemical synthesis, the biosynthesis of VB6 has significant advantages in terms of non-toxicity, high purity, and sustainability, and has great potential for application. Although high-level production of VB6 by microbial cell factories is still in its infancy, in-depth research on the metabolic pathways, key enzymes and homeostatic regulation of VB6 biosynthesis will gradually increase the yield of VB6, and it is expected to fundamentally replace chemical synthesis. This article mainly reviews the physiological functions, chemical synthesis, and biosynthesis of VB6, focusing on the metabolic pathways and homeostatic regulation involved in biosynthesis. It proposes relevant strategies for the development of high-yielding VB6 strains, with the aim of exploring the potential of VB6 biosynthesis and providing a reference for the efficient biosynthesis of VB6.
Key words: Vitamin B6    Pyridoxal phosphate    Chemical synthesis    Biosynthesis    Control of homeostasis
收稿日期: 2023-10-18 出版日期: 2024-04-30
ZTFLH:  Q819  
基金资助: * 福建省自然科学基金(2021J01170);福建省自然科学基金(2021J01172);中国博士后科学基金(2020M670495)
通讯作者: ** 电子信箱:kechr@fjnu.edu.cn;npkace@fjnu.edu.cn   
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周楚然
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引用本文:

周楚然, 王美玲, 黄建忠, 柯崇榕, 杨欣伟. 维生素B6的生理活性与合成的研究进展*[J]. 中国生物工程杂志, 2024, 44(4): 88-101.

ZHOU Churan, WANG Meiling, HUANG Jianzhong, KE Chongrong, YANG Xinwei. Advances in Physiological Activities and Synthesis of Vitamin B6. China Biotechnology, 2024, 44(4): 88-101.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2310023    或    https://manu60.magtech.com.cn/biotech/CN/Y2024/V44/I4/88

图1  维生素B6六种形式分子结构式
图2  维生素B6的生理功能
图3  VB6的化学合成途径 A:Firestone等(左)及周后元等(右)以噁唑法合成PN·HCl线路图 B:吡啶酮法合成PN·HCl线路图 C:炔基醚法合成PN·HCl线路图
Substrates Time/year Product yield/% References
Oxalic acid and Alanine 1994 56 [41]
4-Methyl-5-oxyethyloxazole and 4,7-dihydro-2-propyl-1,3-dioxepin 2012 81.6 [36]
4-Methyl-5-ethoxy-oxazole 2013 86.05 [43]
Cis-2-Butene-1,4-diol and cyclohexane 2019 98.3 [45]
2-Cyano-2-Cibutene-1,4-diol 2020 86.4 [49]
4-Ethoxyoxazole and Isopropyl dioxane 2021 83.2 [50]
4-Methyl-5-ethoxy-2-oxazole 2022 99.52 [48]
表1  噁唑法生产PN·HCl的比较
图4  VB6的生物合成途径 A:DXP依赖途径 B:DXP非依赖途径 C:挽救途径
图5  潜在新途径合成VB6[4]
Organism Medium Vitamer Titer/
(mg·L-1)		 Time/h References
Klebsiella strain MM, CAA PM 2 60 [81]
Saccharomyces marxianus (NRRL-Y-1550) MM PL,PN 2 167 [82]
Achromobacter cycloclastes A.M.S.6201 MM+CAA Vitamin B6 3~4 36~42 [83]
Vibrio strain M-31 Peptone, glycerol, salts Vitamin B6 5 100 [84]
Flavobacterium strain 238-7 Peptone, glycerol, salts, Mn Vitamin B6 18 70 [84]
Bacillus strain MM Vitamin B6 2~5 96 [85]
Saccharomyces microsporn NRRL Y-1550 MM PN 3.3 168 [86]
Pichia guilliermondii Wickerham NK-2 strain MM phosphate, yeast extract et. Vitamin B6 25 168 [87]
S. meliloti IFO 14782 MM,sulfates, yeast extract Vitamin B6 84
(PN为79)		 168 [72]
表2  天然菌株合成VB6
Organism Genotype Vitamer Titer/
(mg·L-1)		 Time/h References
Sinorhizobium meliloti IFO 14782 EcpdxA, EcpdxJ PN 1.74 2 [88]
Escherichia coli BspdxS/T PMP,PM,PL and PN 61 48 [79]
Escherichia coli Ecepd, EcpdxJ, Ecdxs PN 78.5 31 [78]
Sinorhizobium meliloti IFO 14782 Ecepd, SmpdxJ PN 1 300 168 [73]
Sinorhizobium meliloti IFO 14782 SmpdxJ PN 362 168 [89]
Sinorhizobium meliloti IFO 14782 SmpdxP, EcpdxJ PN 149 216 [74]
Bacillus subtilis EcpdxA, SmpdxJ PN 54 72 [76]
Bacillus subtilis EcpdxA, SmpdxJ PN 65 72 [90]
Escherichia coli EcpdxJ, Eczwf, Ecdxs PLP 2 320 12 [80]
Escherichia coli EcpdxA, EcpdxJ, Smdxs, Gniepd,
EcpdxB, SmpdxP		 PN 1 400 48 [54]
表3  工程菌株生产VB6
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