1、orintermediatesforimportantsyntheticproducts.它们可以作为有价值的先导结构,他们常常作为重要的合成产品的起始原料或中间体产品。5:Table 1 gives an overview of the different methods for obtaining pharmaceutical agents. 表1列出了获取药物制剂的不同方法的概述。6. Several therapeutically significant natural products which were originally obtained from natural sourc
2、es are today more effectively -i.e. more economically -prepared by total synthesis.最初从天然资源库获得的几个重要治疗作用的天然产品,今天可以通过全合成更有效地,即更经济地被制备出来。7.Such example include L-amino acids, Chloramphenicol , Caffeine, Dopamine, Epinephrine, Levodopa, peptide hormorres, Prostaglandins, D-Penicillamine, Vincamine, and p
3、ractically all vitamins. 这样的例子包括L-氨基酸、氯霉素、咖啡因、多巴胺、肾上腺素、左旋多巴、肽类激素、前列腺素、D -青霉胺、长春胺,以及几乎所有的维生素。8.Over the last few years fermentationi.e. microbiological processeshas become extremely important.在过去的几年里,发酵,即微生物过程,变得极其重要。9.through modern technology and results from genetic selection leading to the creati
4、on of high performance mutants of microorganisms, fermentation has already become the method of choice for a wide range of substances.通过现代技术和基因选择导致的微生物的高性能突异变种的结果,发酵已成为选择宽范围物质的方法。10.BothEukaryonts(yeastsmoulds)Prokaryonts(singlebacterialcells,andactinomycetes)usedmicroorganisms. 真核细胞(酵母菌和霉菌)和原核细胞(单细
5、胞细菌,放线菌)都可用作微生物。11.The following product types can be obtained: 1. cell material (single cell protein), 2. enzymes,3. primary degradation products (primary metabolites)下列产品类型可以得到:1。细胞的物质(单细胞蛋白),2。酶,3。初级降解产物(初级代谢物),4。二级降解产物(次生代谢物)。 12:Disregardingtheproductionofdextranfrommucousmembranescertaine.g.Le
6、uconostocmesenteroidesclass23relevantonespreparationdrugs.尽管从诸如肠膜状明串球菌的某些微生物的黏膜可以生产葡萄聚糖,但第2和3类产品类型只与药品生产的有关。13Dextran itself , with a molecular weight of 50,000100,000, is used as a blood plasma substitute.葡聚糖自身的分子量5万10万,可用作血浆代用品。14.AmongprimarymetabolitesL-aminoacidsmutants Corynebacteriumglutamicu
7、mBrevibacteriumflavumespecially interesting.而来自谷氨酸棒杆菌和黄色短杆菌突变体的初级代谢产物中,L-氨基酸尤其令人感兴趣。15.From these organisms some 350000 tones of monosodium L-glutamate (food additive)and some 70000 tones of L-lysine(supplement for vegetable proteins)are produced. 从这些生物体中,可以生产约35万吨L-谷氨酸单钠盐(味精,食品添加剂)和约70,000吨L-赖氨酸(用于
8、植物蛋白补充物质)。16Further important primary metabolites are the purina nucleotides,organic acids, lactic acid,citric acid,and vitamins,for example vitamin B,12 from Propionibacterium shermanii.此外,重要的初级代谢产物还有嘌呤核苷酸、有机酸、乳酸、柠檬酸和维生素,例如源自谢氏丙酸杆菌的维生素B12。17、Among the secondary metabolites the antibiotics must be m
9、entioned first.在次生代谢产物中首先必须提到的是抗生素。18、The following five groups represent a yearly worldwide value of US-17 billion:以下五组药品代表了全球每年价值170亿美元:penicillins (Penicillium chrysogenum),青霉素(青霉)cephalosporins (Cephalosporium acremonium),头孢菌素(头孢枝顶)tetracyclines (Streptomyces aureofaciens),四环素(金色链霉菌)erythromycin
10、s (Streptomyces erythreus),红霉素类(红霉素链霉菌)aminoglycosides(e.g.streptomycin from Streptomyces griseus).氨基糖苷类(如 链霉素从灰色链霉菌)19.About 5000 antibiotics have already been isolated from microorganisms, but of these only somewhat fewer than 100 are in therapeutic use.从微生物中已分离出约5000种抗生素,但其中只有不到100种有治疗用途。20.It mu
11、st be remembered,however that many derivatives have been modified by partial synthesis for therapeutic use some 50,000 agents have been semisythetically obtained from -lactams alone in the last decade.但是,必须记住,许多衍生物已通过部分合成法来修饰以获得治疗用途;在过去的十年里,采用半合成方法已从-内酰胺获得了约50,000种制剂。21. To avoid contamination of th
12、e microorganisms with phages etc , the whole process has to be performed under sterile conditions.为了避免受到噬菌体等微生物的污染,(发酵)全过程都必须在无菌条件下进行。22. Fermentations are carried out in stainless steel fermenters with volumes up to 400 m3.发酵是在体积高达400m3的不锈钢发酵罐中进行。23.Since the more important fermentations occur excl
13、usively under aerobic conditions a good supply of oxygen or air(sterile)is needed.由于更重要的是,发酵只在有氧条件下才能发生;因此,需要提供有足够量的氧气或(无菌)空气。23.Carbon dioxide sources include carbohydrates ,e.g. molasses, saccharides, and glucose.二氧化碳的来源包括糖类(碳水化合物),如废糖浆、低聚糖类和葡萄糖。24.Additionally the microorganisms must be supplied
14、in the growth medium with nitrogen-containing compounds such as ammonium sulfate, ammonia , or urea , as well as with inorganic phosphates.另外,微生物必须要培养在有含氮化合物的生长培养基中,例如,硫酸铵,氨水或者尿素,也需要无机磷酸盐。24. Furthermore,constant optimal pH and temperature are required.此外,必需有的恒定的最适pH值和温度。25.In the case of penicillin
15、 G , the fermentation is finished after 200 hours , and the cell mass is separated by filtration.以青霉素G为例,发酵过程在200小时后完成,细胞群经过滤而分离。26. The desired active agents are isolated from the filtrate by absorption or extraction processes 从滤液中经吸收或提取工艺而分离出所需要的活性制剂。利用吸附或者萃取工艺将需要的活性物质从滤液中分离。27.The cell mass, if n
16、ot the desired product, can be further used as an animal feedstuff owing to its high protein content.细胞群,如果并非目的产品,由于其高蛋白质含量,可进一步用作动物饲料 。28.By modern recombinant techniques microorganisms have been obtained which also allow production of peptides which were not encoded in the original genes. 利用现代重组技术
17、,已获得的微生物可以生产原始基因中并未编码的多肽。利用现代的重组技术,可以获得能够生产其本身没有编码该基因的肽类的微生物。29.Modified E.coli bacteria make it thus possible to produce Aand Bchains of human insulin or proinsulin analogs 修饰过的大肠杆菌使得产生人类胰岛素或前胰岛素原类似物的A-和B-链成为可能。30.The disulfide bridges are formed selectively after isolation ,and the final purificat
18、ion is effected by chromatographic procedures.经分离后再选择性形成二硫键,其最终提纯由色析(谱)工序来实现。胰岛素分离后可以选择性地形成二硫键,最终的提纯可以通过色谱分离过程实现。31.In the way human insulin is obtained totally independently from any pancreatic material taken from animals.通过这种方式,完全可以不受限制地从任意的动物胰腺原料获得人类胰岛素。利用这种方法可以完全不依赖任何动物来源的胰腺材料获得人胰岛素。32.Other imp
19、ortant peptides ,hormones ,and enzymes, such as human growth hormone(HGH),neuroma give peptides, somatostatin, interferons, tissue plasminogen activator(TPA), lymphokines ,calcium regulators like calmodulin, protein vaccines ,as well as monoclonal antibodies used as diagnostics ,are synthesized in t
20、his way.其他重要的肽,激素和酶,如人生长激素(HGH),神经活性肽,生长抑素,干扰素,组织纤溶酶原激活剂(TPA),淋巴因子,钙调节剂如钙调蛋白,蛋白疫苗,以及作为诊断用的单克隆抗体,也是采用这种方法合成的。33.Theenzymesenzymaticsystemswhichpresentinasinglemicroorganismbedirectedstereospecificregiospecificchemicalreactions.在单一的微生物中所存在的酶或酶系统可用于定向的立体专一性和区域专一性的化学反应。在单细胞微生物中存在的酶或酶体系可以用于定向的立体选择性和区域选择性
21、的化学反应。34.This principle is especially useful in steroid chemistry.这个原理在类固醇化学反应中特别有用。35、Here we may refer only to the microbes in eleven to 11 hydroxy progesterone xylation hydropower, a key product in the synthesis of cortisone这里我们仅仅只提及黄体酮的微生物11-位羟基化反应制得11-羟基黄体酮,一种用于合成可的松的关键产品。这里我们仅仅涉及黄体酮的微生物11-a-羟基
22、化生成11-a-羟基黄体酮,11-a-羟基黄体酮是一种合成可的松的关键产品。36.Isolatedimportant today notonlybecauseimportancesaccharificationtechnologystarchisomerizationglucosetofructose。如今分离出的酶很重要的,不仅因为淀粉的酶法糖化技术和葡萄糖异构化成果糖的重要性 。如今分离的酶是重要的,不仅仅因为酶催化的淀粉的糖化和葡萄糖到果糖的异构化技术方面的重要性,37.Theyalsosignificantcountlesstestproceduresdiagnosingillness
23、,andanalysisismonitoringtherapy它们在大量诊断疾病的检测程序和监测治疗的酶法分析过程中也很重要。38.A number of enzymes are themselves used as active ingredients.许多酶本身可以被作为活性成分。39,Thuspreparationscontainingproteases(e.g.chymotrypsin,pepsin,andtrypsin),amylaseslipases,mostlycombinationwithantacids,promotedigestion因此,包含蛋白酶(如胰凝乳蛋白酶,胃蛋白
24、酶和胰蛋白酶),淀粉酶和脂肪酶的制剂产品,大多与合成的抗酸剂相配合以促进消化。40,StreptoKinaseurokinasethrombolytics,andasparaginasecytostanticagenttreamentleukemia 链激酶和尿激酶在溶解血栓剂中是重要的,而天冬酰胺酶用作治疗白血病中的细胞生长抑制剂。41,Finallymentionmustmadeusebiocatalystsreactionswheretheirstereospecificityselectivity. 最后提到的一定是酶作为生物催化剂在化学反应中的应用,在化学反应中,酶的立体专一性和选择
25、性可以被使用。42.KnownexamplescleavageracematesN-acety-D,L-aminoacidgiveacids the production of 6-aminopenicillanic acid from benzylpenicillin by means of penicillinamidase and the aspartase-catalysed stereospecific addition of ammonia to fumaric acid in order to produce L-aspartic acid.著名例子有酶裂解N-乙酰基-D,L-氨
26、基酸的外消旋体而生成L-氨基酸,从苄基青霉素经青霉素酰胺酶作用生产6-氨基青霉烷酸,以及天门冬氨酸酶催化立体专一性的氨水和反丁烯二酸加成反应以生产L-天门冬氨酸。43.In these applications the enzymes can be used in immobilized forms somehow bound to carriers- and used as heterogeneous catalysts.在这些应用中,酶可以以某种方式连接在载体上,以固定化的形式来使用,也可以用作多相催化剂。44.This is advantageous because they can t
27、hen easily be separated from the reaction medium and recycled for further use.因为固定化酶可以很容易从反应介质中分离并回收再利用,这是固定化酶的优势。45.Another important process depending on the specific action of proteases is applied for the production of semisynthetic human insulin。依赖于蛋白酶的特殊功能的另一个重要工艺是应用于半合成人胰岛素的生产。46.This starts w
28、ith pig insulin in which the alanine in the 30-position of the-chain is replaced by a threonine tert -butyl ester by the selective action of trypsin.这从猪胰岛素开始,其中在链的30-位的丙氨酸由于胰蛋白酶的选择性作用下被苏氨酸叔丁基酯替换。47.Thisinsulinesterseparated,hydrolyzedhumanfinallypurifiedchromatographic这种被分离的胰岛素酯,水解为人胰岛素,最后经色谱层析过程而纯化。48. Sources for enzymes include not only microorganisms but also vegetable and animal mater
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