共查询到19条相似文献,搜索用时 156 毫秒
1.
2.
3.
环磷酸腺苷(3',5'-cyclic adenosine monophosphate,cAMP)是普遍存在于生物机体内并起着十分重要作用的生理活性物质,称为第二信使。cAMP于1957年被首次发现报道,随后因为它在生命活动中的特殊地位和作用而被大量研究,外源性cAMP早在上世纪70年代就已开发成人类临床药物,在动物生产领域也有极大的潜在应用价值。目前已知临床用cAMP原料药全部由化学法合成。而微生物发酵法生产菌种则以节杆菌、枯草芽孢杆菌和酵母为代表;运用代谢调控机理和技术,用节杆菌发酵生产cAMP的产量据报道已达≥7.23 g/L,用枯草芽孢杆菌也已达到6~7g/L,而酵母作为典型的模式生物,虽然cAMP-PKA信号转导途径基础研究历史悠久,但发酵生产cAMP则近几年才有报道。目前,除了进一步改造菌株、优化发酵技术提高产量和解决分离提纯问题外,充分发挥微生物发酵法的潜力和优势、弥补化学法合成的不足,是赢得其产业化契机的关键。 相似文献
4.
5.
6.
S-腺苷甲硫氨酸(S-adenosyl-l-methionine, SAM)广泛存在于生物体内,主要参与生物体内的转甲基过程、转硫过程及转氨丙基过程,具有重要的生理功能,其生产备受重视。目前SAM生产的研究主要集中于微生物发酵法,该方法与化学合成法和酶催化法相比,成本较低且更容易实现工业化生产。随着需求量的迅速增加,通过菌种改良提高SAM产量备受关注。当前SAM生产菌种改良的主要策略包括常规育种和代谢工程。本文综述了提高微生物生产SAM能力的近期研究进展并探讨了SAM生产中的瓶颈问题及解决方法,以期为进一步提高SAM产量提供思路。 相似文献
7.
C4二元羧酸(苹果酸、延胡索酸和琥珀酸等)是TCA循环中重要的中间代谢产物,广泛用于食品、医药和化工等行业。由于市场潜在需求量巨大,微生物发酵法生产C4二元羧酸备受关注。从自然界筛选的微生物可以大量积累C4二元羧酸,但存在诸多问题。而利用模式微生物生产C4二元羧酸具有很多优势,已成为国内外的研究热点。从三个方面综述了C4二元羧酸的研究进展:利用自然筛选及改造的微生物生产C4二元羧酸,代谢工程改造模式微生物生产C4二元羧酸,C4二元羧酸的发酵生产的代谢调控。最后,提出了微生物发酵法生产C4二元羧酸今后要解决的问题和发展方向。 相似文献
8.
9.
L-丝氨酸及L-半胱氨酸在食品、医药和化妆品等行业有着广泛的应用,在植物和微生物中两者从头合成的前体物均为3-磷酸甘油酸。微生物发酵生产这两种氨基酸以其社会、经济及环境效益展现出良好的前景。针对近年来微生物发酵法生产L-丝氨酸及L-半胱氨酸的研究成果,本文综述了当前国内外学者在该领域研究的热点,即代谢途径及其调节、相关氨基酸的转运及运输、菌种及菌株改造、新菌种的开发等。最后结合当前生物技术的新发展,对今后的研究方向进行了展望。 相似文献
10.
11.
为提高树干毕赤酵母发酵生产琥珀酸的产量,借助基因组规模代谢网络模型iTL885获得琥珀酸合成的最佳代谢途径为扩增icl1基因和敲除sdh1基因。在此基础上,借助代谢工程策略构建过量表达异柠檬酸裂解酶基因icl1的重组菌株FPLicl、缺失琥珀酸脱氢酶基因sdh1的重组菌株FPLΔsdh和缺失sdh1基因同时过量表达icl1基因的重组菌株FPLΔsdh-icl。结果表明:3株重组菌的异柠檬酸裂解酶活性由0.33 U/mg分别增加为1.6、5.6和6.6U/mg;而琥珀酸脱氢酶活性则从13.8 U/mg分别降为10.7、0.3和0.3 U/mg。在以木糖为C源的培养基中,3株重组菌生产琥珀酸的能力分别是0.30、1.20和1.60 g/L。 相似文献
12.
Highly selective production of succinic acid by metabolically engineered Mannheimia succiniciproducens and its efficient purification 下载免费PDF全文
Sol Choi Hyohak Song Sung Won Lim Tae Yong Kim Jung Ho Ahn Jeong Wook Lee Moon‐Hee Lee Sang Yup Lee 《Biotechnology and bioengineering》2016,113(10):2168-2177
13.
Metabolic flux analysis for succinic acid production by recombinant Escherichia coli with amplified malic enzyme activity 总被引:3,自引:0,他引:3
A pfl ldhA double mutant Escherichia coli strain NZN111 was used to produce succinic acid by overexpressing the E. coli malic enzyme. Escherichia coli strain NZN111 harboring pTrcML produced 6 and 8 g/L of succinic acid from 20 g/L of glucose in flask culture at 37 degrees C and 30 degrees C, respectively. When NZN111(pTrcML) was cultured at 30 degrees C with intermittent glucose feeding the final succinic acid concentration obtained was 9.5 g/L and the ratio of succinic acid to acetic acid was 13:1. This system could not be analyzed by conventional metabolic flux analysis techniques, since some pyruvate and succinic acid were accumulated intracellularly. Therefore, a new flux analysis method was proposed by introducing intracellular pyruvate and succinic acid pools. By this new method the concentrations of intracellular metabolites were successfully predicted and the differences between the measured and calculated reaction rates could be considerably reduced. 相似文献
14.
Soon Ho Hong 《Biotechnology and Bioprocess Engineering》2007,12(2):73-79
Succinic acid is a cellular metabolite belonging to the C4-dicarboxylic acid family, and the fermentative production of succinic
acid via the use of recombinant microorganisms has recently become the focus of an increasing amount of attention. Considering
the difficulty inherent to the direct application of natural succinic acid producers to the industrial process, a variety
of systems biology studies have been conducted regarding the development of enhanced succinic acid production systems. This
review shows how the metabolic processes of microorganisms, includingEscherichia coli andMannheimia succiniciproducens, have been optimized in order to achieve enhanced succinic acid production. First, their metabolic networks were constructed
on the basis of complete genome sequences, after which their metabolic characteristics were estimated viain silico computer modeling. Metabolic engineering strategies were designed in accordance with the results ofin silico modeling and metabolically engineered versions of bothE. coli andM. succiniciproducens have been constructed. The succinic acid productivity and yield obtained using metabolically engineered bacteria was significantly
higher than that obtained using wild-type bacteria. 相似文献
15.
Ahmed Zahoor Felix T. F. Küttner Lars M. Blank Birgitta E. Ebert 《Engineering in Life Science》2019,19(10):711-720
Dicarboxylic acids are important bio‐based building blocks, and Saccharomyces cerevisiae is postulated to be an advantageous host for their fermentative production. Here, we engineered a pyruvate decarboxylase‐negative S. cerevisiae strain for succinic acid production to exploit its promising properties, that is, lack of ethanol production and accumulation of the precursor pyruvate. The metabolic engineering steps included genomic integration of a biosynthesis pathway based on the reductive branch of the tricarboxylic acid cycle and a dicarboxylic acid transporter. Further modifications were the combined deletion of GPD1 and FUM1 and multi‐copy integration of the native PYC2 gene, encoding a pyruvate carboxylase required to drain pyruvate into the synthesis pathway. The effect of increased redox cofactor supply was tested by modulating oxygen limitation and supplementing formate. The physiologic analysis of the differently engineered strains focused on elucidating metabolic bottlenecks. The data not only highlight the importance of a balanced activity of pathway enzymes and selective export systems but also shows the importance to find an optimal trade‐off between redox cofactor supply and energy availability in the form of ATP. 相似文献
16.
进化代谢选育高渗透压耐受型产琥珀酸大肠杆菌 总被引:1,自引:0,他引:1
在以碳酸钠为酸中和剂的大肠杆菌两阶段发酵产琥珀酸的过程中,由于Na+的积累造成发酵体系中渗透压的提高,严重抑制了琥珀酸的产物浓度。为了增强大肠杆菌对渗透压的耐受性,考察了利用进化代谢方法筛选高渗透压耐受型高产琥珀酸大肠杆菌菌株的可行性。进化代谢系统作为一种菌株突变装置,可以使菌体在连续培养条件下以最大的生长速率生长。以NaCl为渗透压调节剂,通过在连续培养装置中逐步提高NaCl浓度使菌体在高渗透压条件下快速生长,最终得到了一株高渗透压耐受型琥珀酸生产菌株Escherichia coli XB4。以碳酸钠为酸中和剂,在7 L发酵罐中利用Escherichia coli XB4进行两阶段发酵,厌氧培养60 h后,琥珀酸产量达到了69.5 g/L,琥珀酸生产速率达到了1.81 g/(L.h),分别比出发菌株提高了18.6%和20%。 相似文献
17.
Apfl ldhA double mutantEscherichia coli strain NZN111 was used to produce succinic acid by overexpressing theE. coli malic enzyme gene (sfcA). This strain, however, produced a large amount of malic acid as well as succinic acid. After the analyses of the metabolic
pathways, thefumB gene encoding the anaerobic fumarase ofE. coli was co-amplified to solve the problem of malic acid accumulation. A plasmid, pTrcMLFu, was constructed, which contains an
artificial operon (sfcA-fumB) under the control of the inducibletrc promoter. From the batch culture of recombinantE. coli NZN111 harboring pTrcMLFu, 7 g/L of succinic acid was produced from 20 g/L of glucose, with no accumulation of malic acid.
From the metabolic flux analysis the strain was found under reducing power limiting conditions by severe reorientation of
metabolic fluxes. 相似文献
18.
琥珀酸作为一种重要的C4平台化合物,广泛应用于食品、化学、医药等领域。利用大肠杆菌(Escherichia coli)发酵生产琥珀酸受胞内辅因子不平衡的影响,存在产率低、生产强度低、副产物多等问题。为此,对不同氧气条件下琥珀酸产量和化学计量学分析发现,微厌氧条件下E.coli FMME-N-26高效积累琥珀酸需要借助三羧酸循环(tricarboxylic acid cycle,TCA)为还原性三羧酸途径(reductive tricarboxylic acid pathway,r-TCA)提供足够的ATP和NADH。通过减少ATP消耗、强化ATP合成、阻断NADH竞争途径和构建NADH回补路径等代谢工程策略,组合调控胞内ATP与NADH含量,获得工程菌株E.coli FW-17。通过发酵条件优化,菌株E.coli FW-17在5 L发酵罐能积累139.52 g/L琥珀酸,比出发菌株提高了17.81%,乙酸浓度为1.40 g/L,降低了67.59%。进一步在1000 L发酵罐中进行放大实验,琥珀酸产量和乙酸浓度分别为140.2 g/L和1.38 g/L。 相似文献