Chapter 2 Metabolic Basis of Product Formation
Chapter 2 Metabolic Basis of Product Formation
基因组学：测序、数据开掘、 生物信息学：统计，数 DNA 未知ORF功能分析 据库连结，类型识别， 细胞过程模拟 功能基因组学 功能基因组技术 个 代谢工程 应用 转录组学：差异基因表达 生物芯片技术 RNA 总体基因调控 理解细胞生长 认识癌症发生 疾病诊断与治疗 药物开发 蛋白组学：蛋白质水平，蛋白质 二维凝胶电泳 建立细胞 蛋白质 相互作用，结构功能 质谱 过程模型 改进细胞工厂 加快发酵过程 开发与优化 代谢物组学：动力学参数代酶及代谢物浓度测定 代谢物 谢途径模型 功能基因组学与代谢工程研究框架
功能基因组学与代谢工程研究框架 DNA RNA 蛋白质 基因组学：测序、数据开掘、 未知ORF功能分析 代谢物 转录组学：差异基因表达 生物芯片技术 总体基因调控 二维凝胶电泳 质谱 蛋白组学：蛋白质水平，蛋白质 相互作用，结构功能 代谢物组学：动力学参数代 酶及代谢物浓度测定 谢途径模型 功能基因组学 功能基因组技术 生物信息学：统计，数 据库连结，类型识别， 细胞过程模拟 代谢工程 应 用 理解细胞生长 认识癌症发生 疾病诊断与治疗 药物开发 建立细胞 过程模型 改进细胞工厂 加快发酵过程 开发与优化
Increasing productivity improving process controllability Integrated bioprocess optimisation Environmental influences Bio-informatics Genomics (DNA sequence) Cell Reactor DSP Transcriptomics (mRNA) Proteomics PRODUCT (proteins) Metabolomics (metabolites) Biocatalyst Integrated bioprocess optimisation
2.1.Metabolic organization Carbon Building Oxygen Nitrogen blocks from Phosphorous Sulfur environment Energy A Cells Energy Amino acids b +S PYRUVATE Precursor Nucleotides molecule 0 0 molecules +△pH anaerobic aerobic Fatty ecids synthesis Reducing 1 →ac power waste m Suger moieties products Primary metablism-an overview
2.1. Metabolic organization Primary metablism – an overview
1GA-3-P HAc 8t5-P Ac-p AcCoA Aldhyde G-6-P 6-P-GA 8u-5-P Ac-P GA-3-PPYRLA1c0h0l -4-P 6可 HAc ②，3-Pent anedione 2.Pant angdiol Ac-P F162P Oa网·-Thna-Ba十[ a-AcHB 6-回1e 19c0r01-3-P-Glyc DHAP GA-3-P Aleahol Active Isopentanol 5.cerevisiae Clycerol-prodneint C000] east LA 3-P-GA CH CHO 0 Beer fermentation ￥al (PDC)L Iactate-producing bacteriun (1) PYR PEP PYR a-AcLA a-KIY (2 A AcCoA But anedione 下coz Propionate Propionibaeterfam CTA AcAcCoA HCHO a-KIC Acetoin AcCoA Urea Yellow wine BtCoA ICA te【sentatio回 Acetone Arg Orn Glua-KG BTA BAC 细胞组成物质合成示意图
细胞组成物质合成示意图
Aerobic energy metabolism Glycolysis: Glucose Pyruvate NADH Respiration: ATP ATP Acetyl-CoA NAD H,O TCA-cycle: NADH 0 ADP C02 Aerobic energy metabolism-a simplified overview.The reduced energy substrate (glucose)is oxidised to pyruvate by NAD in a series of reactions called glycolysis.this generates a small amount of the energy carrier ATP.Pyruvate is further oxidised to Co2 by co- enzymes (NAD)in the TCA-cycle.The reduced coenzymes(NADH)are re-oxidised NAD*) in the respiratory chain,where molecular oxygen is the ultimate receiver of the electron.This oxidation is coupled to generation of a relatively large amount of ATP. In anaerobic respiration,nitrate,sulphate or some other oxidised specie is used as electron acceptor instead of molecular oxygen.In fermentative energy metabolism,the NADH from the glycolysis is reoxidised by reduction of pyruvate to fermentation products like ethanol,lactate etc.(Fig 4.6-4.7)
Aerobic energy metabolism
Inositol Gi CTP T RHA Glycogen P DHA ,一G1ca2司 GIP 61n Gla His Proteins---AAs -162四 CoQ] 3-P-GIye SerTrD 四∠3-p-G1y DBAp一GA3P E-4-P PAB ph回 fungi Cys..Ser 3-P-GA DAHP -horismate-☑言网 四 GOA Ala PEP a国 PTA 园G亩sm PHB PYR a-KIV Leu AcCoA C卫一回一p AcCoA RCO-ACP 3-P-clye Lipid PL dr回V PIR ASA 0A6 CTA DDp但o题o-Se王 IsoprenoidCoQ FAs G08 ICA Lys fungi Thr 一Pxo DAP SCA IC ScCoAa-KG G1 D网一Cisp a 80 PorphyrinCtychro图 GIn re回与yiar图 能量代谢副产物合成示意图
能量代谢副产物合成示意图
2.2.Metabolic regulation Catabolism CAnabolism> Macromolecules> Induction and Feed back Individual Catabolite Input inhibition Input mechanisms rate rate repression for various and macro- Constitutive molecules enzymes Repression of Consumption Global Overflow enzymes rate regulatory metabolism systems Principles of regulation of metabolism
2.2. Metabolic regulation Principles of regulation of metabolism
2.3.Catabolic regulation 1 Aerobic energy metabolism in aerobic and facultative organisms 2 The phosphotransferase system of E.coli. Glucose-P →Enz III9 PEP Enz PYR The phosphoenolpyruvate:sugar phosphotransferase system of E.coli.Enz I =Enzyme I,Hpr-Heat stable protein;EnzⅢglc=EnzymeⅢ，soluble enzyme,. specific for glucose;Enz IIglc Enzyme II,membrane bound glucose specific permease
2.3. Catabolic regulation ① Aerobic energy metabolism in aerobic and facultative organisms ② The phosphotransferase system of E.coli
Interaction between PTS and initial metabolism Glucose Cell membrane HMS← Glucose-6-P Fructose-1,6-P 2 PEP PYR
Interaction between PTS and initial metabolism