3.Regulation of transport and initial catabolism by PTS 4.Overflow metabolism 1/2 Glucose NAD* -ADP NAD NADH NADH ◆ATP C02 Ethanol Pyruvate ADH PDC f----------- cytosol mitosol NAD Ald DH Pyruvate NAD+ NADH PDH NADH ATP CO2 Acetate A COAS ATP ADP NAD 3NADH +FADH TCA 2C0 FAD H20302 ATP Energy metabolism of S.cerevisiae.At low rate of glycolysis all pyruvate is completely oxidised to CO,in the TCA cycle.When the glycolysis rate exceeds a critical value, part of the pyruvate is reduced to ethanol.If ethanol is present and the rate of glycolysis is below the critical value,ethanol is consumed and converted to acetylCoA via acetate PDC:pyruvate decarboxylase,ADH alcohol dehydrogenase,AldDH:aldehyde dehydrogenase,ACoAS:Acetylcoenzyme A synthase,PDH:pyruvate dehydrogenase
③. Regulation of transport and initial catabolism by PTS ④. Overflow metabolism
Metabolic balancing A YB Induction Repression Svstem of Mass Ralances: > Overflow 3+v5-45 vl=-IA 「-10 00 0 07 Feed back v2 vl-v3net vi-u 1-1-1 0 0 v4 rC v3net rt-a Finding:bottleneck 001-1 0 v5 vl-rD-a 0 100 -1 D v5 =rE rC-a 0 0 0 0 - .a=1v3+)-(v3-引 Fig.3.1.Using only extracellular accumulation rate measurements,structural singularities like reversible reactions cannot be resolved.The forward and backward directions of a reversible reaction correspond to linearly dependent columns of the stoichiometric matrix,as it is shown for reversible reaction 3 in the network above.Note that,in the depicted network,another source of singularity are the two competing pathways B-C and B-D-E-C.The flux split ratio at B cannot be determined from metabolite balancing(rank(S)=4,2 degrees of freedom and one redundant equation)
Metabolic balancing ➢ Induction ➢ Repression ➢ Overflow ➢ Feed back ➢ Finding:bottleneck
Overflow metabolism Glucose concentration exceeds a critical value >Result: Yeast ethanol glucose effect,30 g/L crabtree effect E.coli:acetic acid Fed-batch
Overflow metabolism ➢ Glucose concentration exceeds a critical value ➢ Result: Yeast :ethanol glucose effect, 30 g/L crabtree effect E.coli: acetic acid ➢ Fed-batch
网络工：以葡萄糖为碳源的代谢网络 以葡萄糖为唯一碳源的代谢网络netl NaDH ATPADP GLC(e) FADH GLC 核苷酸和RNA- 磷酸戊糖途径 fra-45 【1w G6P- -Ru5PPRPP R5P+ 【1 a 21 1、 网络组成： GOHie) F6P+- X5P HIS-------- E4P 67个反应、 GOH- GA3P- 3 GLY SER- 68个代谢物 PG TYR PHE- PYR(e)PEP CHr TRP GSH -ALA ETOH PYR 2、无乙醛酸循环 ACET·- -a-KI VAL LEU- ETOH(e) AC AcCoA ·脂肪酸 T5758 ASN ASP OAA ICI PRO -MET← HSER MAL a-KG GLu ARG CYS+ T16 TaLYS SUC T15 GLN------ -ILEa THR TCA循环 生物量
网络Ⅰ：以葡萄糖为碳源的代谢网络 1、网络组成： 67个反应、 68个代谢物 2、无乙醛酸循环