Pub Date : 2001-07-01DOI: 10.1080/02648725.2001.10648012
S. Nishikawa, Y. Murooka
5-Alninolevulinic acid (ALA) is knovn as a C0l11ffiOIl precursor of tetrapyrrole C0111pounds (e.g. chlorophyll, henle and vitamin Bl~) in all living organisJns (Figure 7. I). ALA has the potential to be widely used as a biodegradable herbicide (Rebeiz et al., 1984), insecticide (Rebeiz et ai., 1988), and in photodynanlic cancer therapy (Kennedy el al., 1990). Recently, Hotta et al. (1997) have reported that a low level of ALA stitnulates plant growth and increases the yields of several crops. ALA also has potential for LIse as an active substrate for the chemical synthesis of nlaterials. For these reasons, a nunlber of ALA production nlethods have been developed. ALA has been synthesized chenlically via selective reduction of acyl cyanides (Pfaltz and Anvar~ 1984) or via dye-sensitized oxygenation ofN-furfurylphthalilnide (Takeya et al., 1989) (Figure 7.2). However, the chenlical synthesis of ALA requires at least four reaction steps and the yield is less than 60%. The high cost ofproductlon of ALA has thus far limited its cOlunlcrcia) utilization. Microorganisills such as Clostridhl111 thernlO{lCeticul1l (Koesnandar et al., 1989), methanogens (Lin et al., 1989), Chlorella spp. (Sasaki et al., 1995: Ano et al., 1999, 20(0). and photosynthetic bacteria (van der Mariet and Zeikus., ]996; Sasaki et al., 1989, 1990, 1993., 1995; Tanaka el al., 1991, 1994a,b) produce ALA in considerable anlounts. The ALA production by photosynthetic bacteria, hovever, requires light illll1nination and has been found to be sensitive to aeration. A crude extract froln
5-丙烯乙酰丙酸(ALA)在所有生物体中都是四吡啶(如叶绿素、汞和维生素Bl~)的前体(图7)。I). ALA作为可生物降解除草剂(Rebeiz et al.， 1984)、杀虫剂(Rebeiz et ai.， 1984)具有广泛应用的潜力。， 1988)，以及光动力癌症治疗(Kennedy等，1990)。最近，Hotta等人(1997)报道了低水平的ALA能促进植物生长并提高几种作物的产量。ALA也有潜力作为LIse的活性底物用于非材料的化学合成。由于这些原因，已经开发了许多ALA生产方法。ALA的化学合成是通过酰基氰化物的选择性还原(Pfaltz和Anvar~ 1984)或n -呋喃基酞胺的染料敏化氧化(Takeya et al.， 1989)(图7.2)。然而，ALA的化学合成至少需要四个反应步骤，收率低于60%。目前，ALA的高生产成本限制了其在国内的应用。微生物如梭状芽孢杆菌(Koesnandar et al.， 1989)、产甲烷菌(Lin et al.， 1989)、小球藻(Sasaki et al.， 1995; Ano et al.， 1999, 20)。以及光合细菌(van der Mariet和Zeikus)。, 996;Sasaki et al.， 1989,1990,1993。, 1995;Tanaka等人，1991,1994a,b)在相当大的范围内产生ALA。然而，光合细菌生产ALA需要光照，并且对曝气很敏感。一种粗提取物
{"title":"5-Aminolevulinic Acid: Production by Fermentation, and Agricultural and Biomedical Applications","authors":"S. Nishikawa, Y. Murooka","doi":"10.1080/02648725.2001.10648012","DOIUrl":"https://doi.org/10.1080/02648725.2001.10648012","url":null,"abstract":"5-Alninolevulinic acid (ALA) is knovn as a C0l11ffiOIl precursor of tetrapyrrole C0111pounds (e.g. chlorophyll, henle and vitamin Bl~) in all living organisJns (Figure 7. I). ALA has the potential to be widely used as a biodegradable herbicide (Rebeiz et al., 1984), insecticide (Rebeiz et ai., 1988), and in photodynanlic cancer therapy (Kennedy el al., 1990). Recently, Hotta et al. (1997) have reported that a low level of ALA stitnulates plant growth and increases the yields of several crops. ALA also has potential for LIse as an active substrate for the chemical synthesis of nlaterials. For these reasons, a nunlber of ALA production nlethods have been developed. ALA has been synthesized chenlically via selective reduction of acyl cyanides (Pfaltz and Anvar~ 1984) or via dye-sensitized oxygenation ofN-furfurylphthalilnide (Takeya et al., 1989) (Figure 7.2). However, the chenlical synthesis of ALA requires at least four reaction steps and the yield is less than 60%. The high cost ofproductlon of ALA has thus far limited its cOlunlcrcia) utilization. Microorganisills such as Clostridhl111 thernlO{lCeticul1l (Koesnandar et al., 1989), methanogens (Lin et al., 1989), Chlorella spp. (Sasaki et al., 1995: Ano et al., 1999, 20(0). and photosynthetic bacteria (van der Mariet and Zeikus., ]996; Sasaki et al., 1989, 1990, 1993., 1995; Tanaka el al., 1991, 1994a,b) produce ALA in considerable anlounts. The ALA production by photosynthetic bacteria, hovever, requires light illll1nination and has been found to be sensitive to aeration. A crude extract froln","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"7 1","pages":"149 - 170"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78284447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-07-01DOI: 10.1080/02648725.2001.10648019
F. Goto, T. Yoshihara, T. Masuda, F. Takaiwa
Iron deficiency resulting from an inadequate diet is a serious nutritional problem. Anaemia derived from iron deficiency causes a host of illnesses, including abortion, brain damage in infants, increased susceptibility to infection, and chronic exhaustion (Baynes and Bothwell, 1990). An estimated 30% of the world's population suffer from some level of iron deficiency, with the highest prevalence found in the developing countries. On the contrary, iron intake by people in developed countries is adequate, and the prevalence of iron deficiency is decreasing. However, anaemia derived from iron deficiency in Japanese females is a concern, and its incidence has remained constant in recent years. There are two approaches to overcome the iron deficiency: one is supplementation of iron to dairy diets, and another is fortification using biological methods. Although supplements added to food or taken in tablet form are effective in preventing and controlling iron deficiency t such treatments are difficult to implement in developing countries because of the associated high costs and lack of primary health care programmes. The other approach is the fortification using biological methods, and there are two ways. The first way is to increase the iron concentration of the hydroponic culture media or soil. This method is costly and cannot accumulate iron to a desirable part of the plant. The second way is to improve the iron content in crops genetically. This way seems better than the first one. This is
{"title":"Genetic Improvement of Iron Content and Stress Adaptation in Plants Using Ferritin Gene","authors":"F. Goto, T. Yoshihara, T. Masuda, F. Takaiwa","doi":"10.1080/02648725.2001.10648019","DOIUrl":"https://doi.org/10.1080/02648725.2001.10648019","url":null,"abstract":"Iron deficiency resulting from an inadequate diet is a serious nutritional problem. Anaemia derived from iron deficiency causes a host of illnesses, including abortion, brain damage in infants, increased susceptibility to infection, and chronic exhaustion (Baynes and Bothwell, 1990). An estimated 30% of the world's population suffer from some level of iron deficiency, with the highest prevalence found in the developing countries. On the contrary, iron intake by people in developed countries is adequate, and the prevalence of iron deficiency is decreasing. However, anaemia derived from iron deficiency in Japanese females is a concern, and its incidence has remained constant in recent years. There are two approaches to overcome the iron deficiency: one is supplementation of iron to dairy diets, and another is fortification using biological methods. Although supplements added to food or taken in tablet form are effective in preventing and controlling iron deficiency t such treatments are difficult to implement in developing countries because of the associated high costs and lack of primary health care programmes. The other approach is the fortification using biological methods, and there are two ways. The first way is to increase the iron concentration of the hydroponic culture media or soil. This method is costly and cannot accumulate iron to a desirable part of the plant. The second way is to improve the iron content in crops genetically. This way seems better than the first one. This is","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"53 1","pages":"351 - 371"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90099058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647995
A. McBain, D. Allison, P. Gilbert
Over the past decade, several strategies have been proposed for the control of surfaceassociated tnicrobial populations. Physical methods, including electrification, ultrasonication, application of ablative laser light and mechanical cleaning or scraping are generally effective at removing sutface growth. Chemical control methods, on the other hand, are often ineffective. This has led to a notorious association of biofilms with resistance towards antibiotics, biocides and disinfectants. In such respects, reaction-diffusion limitation of the passage of oxidizing biocides and antibiotics, across biofilms aided by the presence ofextracellular enzymes often causes the failure of such agents to sanitize contaminated surfaces. Deep-lying cells within biofilms are often also severely nutrientand oxygen..litnited, causing the expression of starvation phenotypes, which include multi-drug efflux pumps and enhanced exopolylner synthesis. During exposure to antimicrobial agents, these slow growing organislns1 being exposed to sub-lethal levels of agent, will generaHy out-survive their less nutrient-depleted congeners. This Inay well enrich the population for drug resistant phenotypes and genotypes during the post...treatment phase. Emerging biofihn treatment methodologies are based 011 our knowledge of biofilm physiology and resistance mechanisms. For example, in an attempt to prevent early colonization of surfaces and in order to overcome reaction..diffusion limitation, treatnlent agents may be coated onto or incorporated into the substrate to be protected. More sophisticated approaches have been developed, with varying success, that deploy erodable~ biocide-containing coatings. Erosion, in this instance being intended to purge the surface of attached bacteria and cellular debris. At the vanguard of emerging control strategies are surface-catalyzed hygiene and anti cell-cell signalling chemicals.
{"title":"Emerging Strategies for the Chemical Treatment of Microbial Biofilms","authors":"A. McBain, D. Allison, P. Gilbert","doi":"10.1080/02648725.2000.10647995","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647995","url":null,"abstract":"Over the past decade, several strategies have been proposed for the control of surfaceassociated tnicrobial populations. Physical methods, including electrification, ultrasonication, application of ablative laser light and mechanical cleaning or scraping are generally effective at removing sutface growth. Chemical control methods, on the other hand, are often ineffective. This has led to a notorious association of biofilms with resistance towards antibiotics, biocides and disinfectants. In such respects, reaction-diffusion limitation of the passage of oxidizing biocides and antibiotics, across biofilms aided by the presence ofextracellular enzymes often causes the failure of such agents to sanitize contaminated surfaces. Deep-lying cells within biofilms are often also severely nutrientand oxygen..litnited, causing the expression of starvation phenotypes, which include multi-drug efflux pumps and enhanced exopolylner synthesis. During exposure to antimicrobial agents, these slow growing organislns1 being exposed to sub-lethal levels of agent, will generaHy out-survive their less nutrient-depleted congeners. This Inay well enrich the population for drug resistant phenotypes and genotypes during the post...treatment phase. Emerging biofihn treatment methodologies are based 011 our knowledge of biofilm physiology and resistance mechanisms. For example, in an attempt to prevent early colonization of surfaces and in order to overcome reaction..diffusion limitation, treatnlent agents may be coated onto or incorporated into the substrate to be protected. More sophisticated approaches have been developed, with varying success, that deploy erodable~ biocide-containing coatings. Erosion, in this instance being intended to purge the surface of attached bacteria and cellular debris. At the vanguard of emerging control strategies are surface-catalyzed hygiene and anti cell-cell signalling chemicals.","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"53 1","pages":"267 - 280"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87462877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647986
J. Yardley, D. Kell, J. Barrett, C. Davey
Introduction All else being equal, the productivity of a biological process is determined by the quantity of biomass present. There is therefore a major requirement for the accurate measurement and control of the biomass within fermentors, at both laboratory and industrial scales. Presently the range of sensors available that can be used in situ and reliably for the monitoring and regulation of biotechnological processes in general is rather limited. These sensors normally rely upon physical (e.g. optical, mechanical and electrical) or chemical variables (e.g. pH and concentration) rather than biological ones per se (Sarra et al., 1996; Pons, 1991). However only physical methods allow the on-line, real-time estimation of biomass (Harris and Kell, 1985). As well as physical methods, any easily determinable chemical that is produced or consumed by cells at an essentially constant rate during cell growth may also be used to assess biomass, e.g. carbon dioxide evolution and oxygen consumption. In these indirect methods biomass is then calculated based upon mass balances, stoichiometric relationships or empirical constants. However, this type of approach has the great disadvantage that it does not generally discriminate between biomass and necromass (Kell et al., 1990). Even if biomass was easily measurable there is still the question of what is biologically relevant information for fermentation control and how can one define and quantify it (e.g. metabolism, viability, vitality, morphology) (Kell et al., 1987; Kell, 1987a;
在其他条件相同的情况下，生物过程的生产率取决于存在的生物量的数量。因此，在实验室和工业规模上，对发酵罐内生物量的精确测量和控制是一个主要的要求。目前，一般来说，可在现场可靠地用于监测和调节生物技术过程的传感器的范围相当有限。这些传感器通常依赖物理(如光学、机械和电气)或化学变量(如pH值和浓度)，而不是生物变量本身(Sarra等人，1996年;脑桥,1991)。然而，只有物理方法允许在线实时估算生物量(Harris和Kell, 1985)。除了物理方法外，细胞在生长过程中以基本恒定的速率产生或消耗的任何易于确定的化学物质也可用于评估生物量，例如二氧化碳演变和氧气消耗。在这些间接方法中，生物量是根据质量平衡、化学计量关系或经验常数来计算的。然而，这种方法有一个很大的缺点，即它通常不能区分生物量和坏死体(Kell et al.， 1990)。即使生物量很容易测量，仍然存在一个问题，即什么是发酵控制的生物学相关信息，以及如何定义和量化它(例如代谢、活力、活力、形态)(Kell等人，1987;凯尔,1987;
{"title":"On-Line, Real-Time Measurements of Cellular Biomass using Dielectric Spectroscopy","authors":"J. Yardley, D. Kell, J. Barrett, C. Davey","doi":"10.1080/02648725.2000.10647986","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647986","url":null,"abstract":"Introduction All else being equal, the productivity of a biological process is determined by the quantity of biomass present. There is therefore a major requirement for the accurate measurement and control of the biomass within fermentors, at both laboratory and industrial scales. Presently the range of sensors available that can be used in situ and reliably for the monitoring and regulation of biotechnological processes in general is rather limited. These sensors normally rely upon physical (e.g. optical, mechanical and electrical) or chemical variables (e.g. pH and concentration) rather than biological ones per se (Sarra et al., 1996; Pons, 1991). However only physical methods allow the on-line, real-time estimation of biomass (Harris and Kell, 1985). As well as physical methods, any easily determinable chemical that is produced or consumed by cells at an essentially constant rate during cell growth may also be used to assess biomass, e.g. carbon dioxide evolution and oxygen consumption. In these indirect methods biomass is then calculated based upon mass balances, stoichiometric relationships or empirical constants. However, this type of approach has the great disadvantage that it does not generally discriminate between biomass and necromass (Kell et al., 1990). Even if biomass was easily measurable there is still the question of what is biologically relevant information for fermentation control and how can one define and quantify it (e.g. metabolism, viability, vitality, morphology) (Kell et al., 1987; Kell, 1987a;","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"6 1","pages":"3 - 36"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80549582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10648001
T. Watts, A. Fasano
In the past few years, we have witnessed an explosion in research aimed at creating new oral drug delivery systelns. This research has been fuelled by unprecedented challenges, such as the need to deliver newer and more complex dnlgs (such as proteins, hormones, etc.) that are becoming available through genetic engineering. Consequently, the need has arisen for further investigation into utilizing the intestine as a pritne site for targeting the absorption on these new compounds. One potential and attractive JnechaniSlll would be to exploit avenues that increase intestinal peJmeability. Theoretically, three transepitheJiaJ pathways are available for the passage of nlolecules fronl the intestinal lumen into the bloodstreanl (Figure 16.1): ( I) transcellular (ie through the cell) canier-mediated active or facil itated transport; (2) transcellular passive transport; and (3) paracellu]ur (ie between adjacent cells) transport With the exception of those molecules that are transported by active or facilitated transcellular mechanisms, the absorption of large hydrophilic macromolecules is mainly lim.ited to the paraceUular pathway (Lee et al., 1991). Under normal conditions, however, this pathway is restricted to molecules with molecular radii < II Angstroms and, therefore, is not accessible to large compounds. To overconle the intestinal barrier, several strategies have been developed to target either the transcellular or the paracellular pathway for drug delivery. The nlost
在过去的几年中，我们目睹了旨在创造新的口服给药系统的研究的爆炸式增长。这项研究受到前所未有的挑战的推动，例如需要通过基因工程提供更新和更复杂的dnlgs(如蛋白质，激素等)。因此，有必要进一步研究利用肠道作为靶向吸收这些新化合物的原始位点。一个潜在的和有吸引力的jnechanll将是开发途径，增加肠道的渗透性。理论上，分子可通过三种途径从肠腔进入血流(图16.1):(I)跨细胞(即通过细胞)罐介导的主动或辅助运输;(2)跨细胞被动转运;(3)细胞旁(即相邻细胞之间)运输除了那些通过主动或促进的跨细胞机制运输的分子外，主要是对大型亲水性大分子的吸收。被诱导到眼旁通路(Lee et al.， 1991)。然而，在正常条件下，这一途径仅限于分子半径< 2埃的分子，因此，大型化合物无法进入。为了克服肠道屏障，已经开发了几种针对跨细胞或细胞旁途径的药物递送策略。的nlost
{"title":"Modulation of Intestinal Permeability: A Novel and Innovative Approach for the Oral Delivery of Drugs, Macromolecules and Antigens","authors":"T. Watts, A. Fasano","doi":"10.1080/02648725.2000.10648001","DOIUrl":"https://doi.org/10.1080/02648725.2000.10648001","url":null,"abstract":"In the past few years, we have witnessed an explosion in research aimed at creating new oral drug delivery systelns. This research has been fuelled by unprecedented challenges, such as the need to deliver newer and more complex dnlgs (such as proteins, hormones, etc.) that are becoming available through genetic engineering. Consequently, the need has arisen for further investigation into utilizing the intestine as a pritne site for targeting the absorption on these new compounds. One potential and attractive JnechaniSlll would be to exploit avenues that increase intestinal peJmeability. Theoretically, three transepitheJiaJ pathways are available for the passage of nlolecules fronl the intestinal lumen into the bloodstreanl (Figure 16.1): ( I) transcellular (ie through the cell) canier-mediated active or facil itated transport; (2) transcellular passive transport; and (3) paracellu]ur (ie between adjacent cells) transport With the exception of those molecules that are transported by active or facilitated transcellular mechanisms, the absorption of large hydrophilic macromolecules is mainly lim.ited to the paraceUular pathway (Lee et al., 1991). Under normal conditions, however, this pathway is restricted to molecules with molecular radii < II Angstroms and, therefore, is not accessible to large compounds. To overconle the intestinal barrier, several strategies have been developed to target either the transcellular or the paracellular pathway for drug delivery. The nlost","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"53 1","pages":"433 - 454"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88422017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647991
L. Tully, B. Levin
The field of human mitochondrial genetics has advanced way beyond where the Hunlan Genome Project hopes to be by the year 2003, the projected year for completing the sequence of the entire human nuclear DNA genome. Not only has the mitochondrial DNA (JntDNA) been completely sequenced, the regions that code for genes and those that are noncoding have been distinguished, the function of all the genes have been determined, the nltDNA genetic code has been shown to differ in some ways from the Universal Genetic Code of nuclear DNA, and a Ilutnber of diseases have been correlated with specific mitochondrial DNA mutations (http:// infinity.gen.emory.edu/mitomap.htmI). Some of the current areas of research interest with regard to mitochondrial genetics are: examining the variability among individuals or within a single individual (heteroplasmy); distinguishing between polymorphisms and disease-producing mutations; detecting mutations present in low concentrations in an individual; analysing the effects of chemical or physical agents and the mechanisms which lead
{"title":"Human Mitochondrial Genetics","authors":"L. Tully, B. Levin","doi":"10.1080/02648725.2000.10647991","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647991","url":null,"abstract":"The field of human mitochondrial genetics has advanced way beyond where the Hunlan Genome Project hopes to be by the year 2003, the projected year for completing the sequence of the entire human nuclear DNA genome. Not only has the mitochondrial DNA (JntDNA) been completely sequenced, the regions that code for genes and those that are noncoding have been distinguished, the function of all the genes have been determined, the nltDNA genetic code has been shown to differ in some ways from the Universal Genetic Code of nuclear DNA, and a Ilutnber of diseases have been correlated with specific mitochondrial DNA mutations (http:// infinity.gen.emory.edu/mitomap.htmI). Some of the current areas of research interest with regard to mitochondrial genetics are: examining the variability among individuals or within a single individual (heteroplasmy); distinguishing between polymorphisms and disease-producing mutations; detecting mutations present in low concentrations in an individual; analysing the effects of chemical or physical agents and the mechanisms which lead","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"25 1","pages":"147 - 178"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85441850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647993
Lilia M. Babél, Christopher J. Linneversl, B. Schmidt
Mammalian endopeptidases and exopeptidases participate in a wide variety of cellular processes. They are responsible for the relatively non-specific degradation of proteins targeted for digestion or recycling, and they also perform highly specific single-site cleavages necessary for the activation or inactivation of functional proteins and peptides. Likewise, numerous viruses that infect mammalian cells utilize virusencoded proteases to regulate their replication cycle. Malnmalian proteases are expressed as enzymatically inactive zymogens requiring specific coor post-translational processing by self or other proteases. Virus...encoded proteases are expressed as part of viral polyproteins that also require specific autoprocessing to release the fully active protease. Thus, the sanle theme is used, where structural motifs prevent the enzyme from being active before the appropriate time and place, and catalytic proficiency is regulated by the formation of the active protease (Babe and Craik, 1997). This theme must be kept in mind when designing heterologous expression systems for mammalian and viral proteases to ensure the production of active or activatable enzymes. Advances in the study of proteases in the past two decades have been largely dependent on the ability of researchers to produce significant quantities of pure enzymes. Generally, recombinant gene expression systems have been used to accomplish this task, especially for proteases that are naturally produced in very limited amounts. Heterologous expression systems also have the advantage of being able to produce variant proteases at will, allowing the study of structure-function relationships and modifications of their properties. In addition to basic research, the production of recolnbinant proteases has been crucial to the development of cOlnmercial products. For example, recombinant bovine chyl11osin. an aspaitic protease, is used in the manufacture of cheese, while
{"title":"Production of Active Mammalian and Viral Proteases in Bacterial Expression Systems","authors":"Lilia M. Babél, Christopher J. Linneversl, B. Schmidt","doi":"10.1080/02648725.2000.10647993","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647993","url":null,"abstract":"Mammalian endopeptidases and exopeptidases participate in a wide variety of cellular processes. They are responsible for the relatively non-specific degradation of proteins targeted for digestion or recycling, and they also perform highly specific single-site cleavages necessary for the activation or inactivation of functional proteins and peptides. Likewise, numerous viruses that infect mammalian cells utilize virusencoded proteases to regulate their replication cycle. Malnmalian proteases are expressed as enzymatically inactive zymogens requiring specific coor post-translational processing by self or other proteases. Virus...encoded proteases are expressed as part of viral polyproteins that also require specific autoprocessing to release the fully active protease. Thus, the sanle theme is used, where structural motifs prevent the enzyme from being active before the appropriate time and place, and catalytic proficiency is regulated by the formation of the active protease (Babe and Craik, 1997). This theme must be kept in mind when designing heterologous expression systems for mammalian and viral proteases to ensure the production of active or activatable enzymes. Advances in the study of proteases in the past two decades have been largely dependent on the ability of researchers to produce significant quantities of pure enzymes. Generally, recombinant gene expression systems have been used to accomplish this task, especially for proteases that are naturally produced in very limited amounts. Heterologous expression systems also have the advantage of being able to produce variant proteases at will, allowing the study of structure-function relationships and modifications of their properties. In addition to basic research, the production of recolnbinant proteases has been crucial to the development of cOlnmercial products. For example, recombinant bovine chyl11osin. an aspaitic protease, is used in the manufacture of cheese, while","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"103 1","pages":"213 - 254"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85838711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647988
J. Holloway, S. Ye, I. Day
The analysis of susceptibility loci for complex genetic diseases has become the focus of much activity in recent years. A key to the successful analysis of these disorders is the analysis of many single nucleotide polymotphisms (SNPs) in extensive population samples to identify DNA variants that are risk factors. As a result, efficient costeffective methods are required for the typing of SNPs. In this review we present an overview of one such method, Microplate-Array Diagonal Gel Electrophoresis (MADGE), and compare it with a number of other methodologies for high throughput SNP typing In disease gene mapping, an essential role is played by the typing of polymorphism between individuals. In the characterization of etiological genetic sites for polygenic disease traits, due to the nature of the genetic contribution to the disease, and thus to the methods of analysis, the number of polymorphic loci needing to be typed is extremely large. Common polymorphism is likely to underpin many common disease susceptibilities. Either guided by linkage studies or by functional hypotheses concerning specific genes, genetic variation in specific genes is examined by association either in family-based or case-control designs (Weeks and Lathrop, 1995). There are two main limitations in the analysis of genetic susceptibility to common disease. The first is that for complex diseases, which have multiple disease-causing
{"title":"Tools for Molecular Genetic Epidemiology: A Comparison of MADGE Methodology with Other Systems","authors":"J. Holloway, S. Ye, I. Day","doi":"10.1080/02648725.2000.10647988","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647988","url":null,"abstract":"The analysis of susceptibility loci for complex genetic diseases has become the focus of much activity in recent years. A key to the successful analysis of these disorders is the analysis of many single nucleotide polymotphisms (SNPs) in extensive population samples to identify DNA variants that are risk factors. As a result, efficient costeffective methods are required for the typing of SNPs. In this review we present an overview of one such method, Microplate-Array Diagonal Gel Electrophoresis (MADGE), and compare it with a number of other methodologies for high throughput SNP typing In disease gene mapping, an essential role is played by the typing of polymorphism between individuals. In the characterization of etiological genetic sites for polygenic disease traits, due to the nature of the genetic contribution to the disease, and thus to the methods of analysis, the number of polymorphic loci needing to be typed is extremely large. Common polymorphism is likely to underpin many common disease susceptibilities. Either guided by linkage studies or by functional hypotheses concerning specific genes, genetic variation in specific genes is examined by association either in family-based or case-control designs (Weeks and Lathrop, 1995). There are two main limitations in the analysis of genetic susceptibility to common disease. The first is that for complex diseases, which have multiple disease-causing","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"4 1","pages":"71 - 90"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88159699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647992
E. Hickman, K. Helin
Cancer is a genetic disease dependent upon the accumulation of mutations within the genes that control cellular proliferation. Mutations may arise, either as a consequence of errors made during DNA replication, or after exposure to physical or chemical mutagens. DNA damaging agents, such as the oxygen free radicals produced by the mitochondria during respiration, are continually generated as a result of normal cellular activity (Kaufmann and Paules, 1996). Disruption of the genes responsible for cell growth regulation, programmed cell death (apoptosis), differentiation and motility may contribute to tumour formation, either promoting unrestrained cell division or allowing inappropriate cell survival. The earliest studies revealed that tumours contain gain-of-function mutations within genes that normally signal cell division under specific growth conditions. The products of these genes are often components of the signal transduction pathways that are either overexpressed or expressed as overactive mutant proteins (Cantley et al., 1991). The constitutive activation of these pathways favours proliferation under conditions that would otherwise be growth prohibitive. However, it is clear that a single oncogenic mutation is insufficient to induce the formation of a tumour. The creation of artificial tumour cell lines by exogenous expression of oncogenes has demonstrated that at least four growth regulatory pathways must be disrupted to enable tumourigenic conversion of primary cells (Hahn et al., 1999). The requirement for additional mutations is explained, at least in part, by the existence of cell cycle checkpoints that have evolved to protect multicellular organisms against tumourigenesis. It is now clear that these checkpoints are governed by a second class of genes, the tumour suppressor genes, which repress cellular proliferation and which are frequently mutated in tumours. In normal tissues, the growth restraint exerted by the tumour suppressor gene products
癌症是一种遗传疾病，依赖于控制细胞增殖的基因中突变的积累。突变可能是由于DNA复制过程中发生的错误，或暴露于物理或化学诱变剂之后。DNA损伤剂，如线粒体在呼吸过程中产生的氧自由基，是正常细胞活动不断产生的结果(Kaufmann和Paules, 1996)。负责细胞生长调节、程序性细胞死亡(凋亡)、分化和运动的基因的破坏可能有助于肿瘤的形成，要么促进无限制的细胞分裂，要么允许不适当的细胞存活。最早的研究表明，肿瘤中含有在特定生长条件下通常发出细胞分裂信号的基因中的功能获得突变。这些基因的产物通常是信号转导途径的组成部分，要么过度表达，要么表达为过度活跃的突变蛋白(Cantley et al.， 1991)。这些途径的本构激活有利于在不利于生长的条件下增殖。然而，很明显，一个单一的致癌突变不足以诱导肿瘤的形成。通过外源性癌基因表达产生的人造肿瘤细胞系表明，至少有四条生长调控途径必须被破坏，才能使原代细胞发生致瘤性转化(Hahn等人，1999)。细胞周期检查点的存在至少在一定程度上解释了对额外突变的需求，细胞周期检查点的存在是为了保护多细胞生物免受肿瘤发生的影响。现在很清楚，这些检查点是由第二类基因控制的，即肿瘤抑制基因，它抑制细胞增殖，并且在肿瘤中经常发生突变。在正常组织中，肿瘤抑制基因产生的生长抑制作用
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Pub Date : 2000-08-01DOI: 10.1080/02648725.2000.10647998
D. Durzan
Metabolic engineering aims to optimize yields of comlnercially valuable products by controlling enzymatic, transport, and cell regulatory functions by indirect or direct genetic intervention. Many natural products from plants on earth are now being metabolically engineered (eg Grotewold et al., 1998; Knauf, 1998; Gnlys et al., 1998). While large-scale culture is technically feasible (Verpoorte el al., 1998), plant cell bioreactors have historically given ecollotnically low and unreliable yields (Alfermann and Petersen, 1995; Fowler, 1988). Shikonin and berberine (Fujita, 1988) raised hopes for products that were eventually not commercially sustainable. The recovery of products froln vacuoles requires harvesting and disruption of cells. Processes are sought where products are released directly into the culture medium. Slow growth and low product levels are major constraints. Space environments offer new opportunities for the metabolic engineering of plant cells. Bioreactor process controls will differ significantly from production facilities on earth because of constraints in gravitational fields, the increased use of small modular designs, and physical Iinlitations to downstream processing capabilities. For the International Space Station (ISS), spacecraft construction and maintenance of crew support systems will initially limit the time for basic and applied research. This review evaluates factors for the development and testing of lTIodels for drug producing plant cells, given the constraints of space environlnents. Mission priorities are given
代谢工程旨在通过间接或直接的基因干预来控制酶、运输和细胞调节功能，从而优化具有商业价值的产品的产量。地球上许多来自植物的天然产物现在正在进行代谢工程(例如Grotewold等人，1998;可耐福,1998;Gnlys et al.， 1998)。虽然大规模培养在技术上是可行的(Verpoorte等人，1998年)，但从历史上看，植物细胞生物反应器的产量在生态上很低，而且不可靠(Alfermann和Petersen, 1995年;福勒,1988)。紫草素和小檗碱(Fujita, 1988)提高了产品最终在商业上不可持续的希望。从液泡中回收产物需要收获和破坏细胞。寻求将产品直接释放到培养基中的工艺。增长缓慢和产品水平低是主要制约因素。空间环境为植物细胞的代谢工程提供了新的机遇。由于重力场的限制、小型模块化设计的使用增加以及对下游处理能力的物理限制，生物反应器的过程控制将与地球上的生产设施有很大不同。对于国际空间站(ISS)来说，航天器的建造和船员支持系统的维护将最初限制基础研究和应用研究的时间。考虑到空间环境的限制，本文综述了用于生产药物的植物细胞的tiodel模型的开发和测试的因素。确定特派团的优先次序
{"title":"Metabolic Engineering of Plant Cells in a Space Environment","authors":"D. Durzan","doi":"10.1080/02648725.2000.10647998","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647998","url":null,"abstract":"Metabolic engineering aims to optimize yields of comlnercially valuable products by controlling enzymatic, transport, and cell regulatory functions by indirect or direct genetic intervention. Many natural products from plants on earth are now being metabolically engineered (eg Grotewold et al., 1998; Knauf, 1998; Gnlys et al., 1998). While large-scale culture is technically feasible (Verpoorte el al., 1998), plant cell bioreactors have historically given ecollotnically low and unreliable yields (Alfermann and Petersen, 1995; Fowler, 1988). Shikonin and berberine (Fujita, 1988) raised hopes for products that were eventually not commercially sustainable. The recovery of products froln vacuoles requires harvesting and disruption of cells. Processes are sought where products are released directly into the culture medium. Slow growth and low product levels are major constraints. Space environments offer new opportunities for the metabolic engineering of plant cells. Bioreactor process controls will differ significantly from production facilities on earth because of constraints in gravitational fields, the increased use of small modular designs, and physical Iinlitations to downstream processing capabilities. For the International Space Station (ISS), spacecraft construction and maintenance of crew support systems will initially limit the time for basic and applied research. This review evaluates factors for the development and testing of lTIodels for drug producing plant cells, given the constraints of space environlnents. Mission priorities are given","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"31 1","pages":"353 - 388"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81894960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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