Chapter 1 Introduction
Chapter 1 Introduction
1.1.History of Industrial Biotechnology Products of fermentation processes Products type Example Products type Example Alcohols Ethanol Butanol Organic acids Citric acid (+acetone) Acetic acid Amino acids Glutamic acid Lysine Polysaccharides Dectran Xanthan Antibiotic Penicillins Purified waste water BOD-removal Tetracyclines Senitrification En☑ymes Proteases Amylases Single-cell protein Fodder yeast Hormones Insulin Human Starter cultures Baker's yeast Lactic growth hormone starters Insecticides Thuringiensin Steroid Cortisone transformation Methane Biogasfrom Vaccines Tetanus sewage/water Nucleotides IMP GMP Vitamins Riboflavin
1.1. History of Industrial Biotechnology Products of fermentation processes Products type Example Products type Example Alcohols Ethanol Butanol (+acetone) Organic acids Citric acid Acetic acid Amino acids Glutamic acid Lysine Polysaccharides Dectran Xanthan Antibiotic Penicillins Tetracyclines Purified waste water BOD-removal Senitrification Enzymes Proteases Amylases Single-cell protein Fodder yeast Hormones Insulin Human growth hormone Starter cultures Baker’s yeast Lactic starters Insecticides Thuringiensin Steroid transformation Cortisone Methane Biogasfrom sewage/water Vaccines Tetanus Nucleotides IMP GMP Vitamins Riboflavin
1.1.1 Era of mioorganisium(19 century-1944) 1857.France Pasteur microorganism 1897.Germany Buchner enzyme A:primary metabolism product:ethanol,citric acid B:anaerobic fermentation 1.1.2 Biochemical Engineering Penicillin production lab:1000mL;40u/ml,recovery35%,purity20%,80000 flask produce 1kg penicillin,16000 $/kg 1941年US and English 1943年化学工程师和生物学家合作 A:通气发酵罐，效价提高到200u/ml B:离心最取齐萃取器，萃取过程连续化，纯度为60%，收率75% 解决：通气、培养基灭菌和分离提取 1944年链霉素 1947年美国麦克尔公司被授予“生物化学工程的专题研究”的麦可老一希尔化 学工程成就奖
1.1.1 Era of mioorganisium(19 century —1944） 1857. France Pasteur microorganism 1897. Germany Buchner enzyme A： primary metabolism product: ethanol, citric acid B: anaerobic fermentation 1.1.2 Biochemical Engineering Penicillin production lab: 1000mL; 40u/ml, recovery35%, purity20%, 80000 flask produce 1kg penicillin, 16000 $/kg 1941年 US and English 1943年 化学工程师和生物学家合作 A: 通气发酵罐，效价提高到200u/ml B: 离心最取齐萃取器，萃取过程连续化，纯度为60%，收率75% 解决：通气、培养基灭菌和分离提取 1944年 链霉素 1947年 美国麦克尔公司被授予“生物化学工程的专题研究”的麦可老—希尔化 学工程成就奖
史 的今 中细 28 9 这是一次偶然的发现，但 它又是人类努力探求的必然 结果 青霉素 ■弗菜明发现了问题：这些霉斑是怎么回事 在死亡中诞生 年型授石密精法出为欧中的
Tiselius开创生物色谱和电泳 Arne Tiselius的贡献 >1925年23岁作为Svedberg研究生 外力场：离心场+电场 >1930年一个电泳：移动界面电泳方法 (Moving boundary method,毕业论文 >1934年两个学生Phipot&Svensson 紫外光光学照像系统：最早的监测器 1935年-1936年投稿3次，都被拒稿
Tiselius 开创生物色谱和电泳 Arne Tiselius的贡献 ➢ 1925年 23岁作为Svedberg研究生 外力场： 离心场+电场 ➢ 1930年 一个电泳：移动界面电泳方法 （Moving boundary method)，毕业论文 ➢ 1934年 两个学生Phipot&Svensson 紫外光光学照像系统：最早的监测器 1935年-1936年投稿 3次，都被拒稿
Professor Arne Tiselius in his chromatography laboratory in the early 1950s. In some experiments he used quartz columns and UV-light to follow the migration of protein zones using a television monitor. Photo:Uppsala Bild/Upplandsmuseet
Professor Arne Tiselius in his chromatography laboratory in the early 1950s. In some experiments he used quartz columns and UV-light to follow the migration of protein zones using a television monitor. Photo: Uppsala Bild / Upplandsmuseet
1.2.Enzyme Engineering >1894 Japan amylase first commercial enzyme 1953 Grubhofer and Schleith immobilization of enzyme 1969 immobilized enzyme in industry to produce amino acid(Japan) The system of enzyme and viable cell immobiliton was coupled amino acid,organic acid,ribonucleotide and antibiotics Novel biotechnologies were applied in enzyme engineering cell fusion and DNA recombination used to improve the strain of enzyme
1.2. Enzyme Engineering ➢ 1894 Japan amylase（first commercial enzyme ） ➢ 1953 Grubhofer and Schleith immobilization of enzyme 1969 immobilized enzyme in industry to produce amino acid(Japan ) ➢ The system of enzyme and viable cell immobiliton was coupled amino acid, organic acid, ribonucleotide and antibiotics ➢ Novel biotechnologies were applied in enzyme engineering cell fusion and DNA recombination used to improve the strain of enzyme
1.3.Genetic Engineering 1974.US Boyer and Cohen recombinant DNA 1976.Genentech first biotechnology company was established 1977.Boyer hGH 1977.W.Gilbert（1978年获诺贝尔化学奖) insulin
1.3. Genetic Engineering 1974. US Boyer and Cohen recombinant DNA 1976. Genentech first biotechnology company was established 1977. Boyer hGH 1977. W.Gilbert（1978年获诺贝尔化学奖） insulin
Some recombinant products that became available by the introduction of the genetic engineering technique Product Origin Producting organism hGH Human Escherichia coli IGF-I Human Escherichia coli IFN-a-2a Human Escherichia coli Protein G Streptococcus Escherichia coli Insulin Human Saccharomyces cerevisiae Hepatitis B vaccine Hepatitis virus Saccharomyces cerevisiae Chymosin Calf Kluyveromyces lactis Lipase Humicola lanuginosa Aspergillus oryzae tPa Human Animal cells Superoxide dismutase Human Animal cells
Product Origin Producting organism hGH Human Escherichia coli IGF-I Human Escherichia coli IFN-α-2a Human Escherichia coli Protein G Streptococcus Escherichia coli Insulin Human Saccharomyces cerevisiae Hepatitis B vaccine Hepatitis virus Saccharomyces cerevisiae Chymosin Calf Kluyveromyces lactis Lipase Humicola lanuginosa Aspergillus oryzae tPa Human Animal cells Superoxide dismutase Human Animal cells Some recombinant products that became available by the introduction of the genetic engineering technique
代谢工程策略 丙酮 碳水化合物 原料 ·利用系统生物学手段，发现 了新的支路途径和调控位点 C6糖-P C3酮 ·设计新的代谢工程策略 (C6糖-P C4醇 C6糖-P (C3酮酸 C2 CoA2-p一C2酸 C3醛P■ C3酮酸P Xc②一② C6酸 C3羟酮-P →C3上醇c4賤 c5酮酸 C4COA*
代谢工程策略 碳水化合物 原料 丙酮 丁醇 C2 酸 C2 醇 C3 酮酸 C2 CoA C2 醛 C2 ~P C3 C3 酮酸~P 酸~P C4 CoA C3 酮 C4 醇 C6 糖~P C3 醛~P C6 糖~P C6 糖~P 利用系统生物学手段，发现 了新的支路途径和调控位点 酸~P C3 羟酮~P C3 二醇 C4 酸 C5 酮酸 C4 CoA C6 酸 设计新的代谢工程策略