Holms H
Robertson Institute of Biotechnology, Glasgow, UK.
FEMS Microbiol Rev. 1996 Dec;19(2):85-116. doi: 10.1111/j.1574-6976.1996.tb00255.x.
The growth of the bacterial cell involves the co-ordination of the fluxes of carbon into a considerable diversity of products that are the components of the cell. Fortunately the monomers from which the cell's polymers are made are themselves synthesised from a relatively small group of precursors that are the products of the central metabolic pathways. This simplification renders cell metabolism accessible to flux analysis, a method for handling experimental data to derive metabolic fluxes. Through such analysis of the growth of Escherichia coli ML308 on 11 single carbon sources in batch, turbidostat or chemostat culture general patterns are discernible. Most significant among these are that growth on different carbon sources is achieved without any obvious enzyme acting as a regulator of metabolic flux, except when acetate is the sole source of carbon. In this case a junction is created at which iso citrate dehydrogenase (ICDH) and isocitrate lyase (ICL) compete for their common substrate and this competition is resolved by partial inactivation of ICDH to match flux through ICL and this balance limits growth rate. In this sense, flux through ICDH and ICL is 'rate-limiting'. Uptake of six of the remaining carbon inputs exceeds the capacity of the central metabolic pathways (CMPs) to sustain flux to the precursors required for growth and the CMPs are balanced by excretion of acetate. Restriction of carbon uptake by chemostat progressively diminishes growth rate and acetate excretion until acetate excretion is prevented. For the four remaining carbon sources, uptake is apparently restricted and the products are biomass, carbon dioxide and water. Carbon sources feeding the phosphorylated parts of the CMPs flux relatively more carbon to precursors (Pre-C) than CO2 when compared with carbon sources which feed into the non-phosphorylated pathways. Pre-C/CO2 ratios for the former are 1.73-3.91 and for the latter are 0.46-0.78. Flux analysis of all 11 carbon sources shows that there is an overabundant supply of 'energy' (ATP + [2H]), generated by the CMPs, in all phenotypes and conditions down to a glucose chemostat at mu of 0.72. This excess energy is a thermodynamic inefficiency which must be dissipated as heat. E. coli ML308 probably evolved in circumstances of 'feast' and 'famine'. The two strategies selected (excretion of surplus carbon and restriction of mu) would appear to be defences against 'feast'. Presumably there are defences against 'famine'. These are not made obvious by flux analysis but allosteric control of irreversible enzymes would protect pools of essential nutrients from rapid depletion on the sudden onset of 'famine'.
细菌细胞的生长涉及将碳通量协调进入种类繁多的产物中，这些产物构成了细胞的组成部分。幸运的是，构成细胞聚合物的单体本身是由相对少量的前体合成的，这些前体是中心代谢途径的产物。这种简化使得细胞代谢能够进行通量分析，通量分析是一种处理实验数据以推导代谢通量的方法。通过对大肠杆菌ML308在分批培养、恒浊器培养或恒化器培养中利用11种单一碳源生长情况的分析，可以看出一些普遍模式。其中最显著的是，在不同碳源上生长时，除了乙酸盐作为唯一碳源的情况外，没有任何明显的酶作为代谢通量的调节因子。在这种情况下，会形成一个节点，异柠檬酸脱氢酶（ICDH）和异柠檬酸裂解酶（ICL）在此竞争它们的共同底物，这种竞争通过ICDH的部分失活得以解决，以匹配通过ICL的通量，这种平衡限制了生长速率。从这个意义上说，通过ICDH和ICL的通量是“限速的”。其余六种碳源的摄取超过了中心代谢途径（CMPs）维持向生长所需前体通量的能力，CMPs通过乙酸盐的排泄来平衡。通过恒化器限制碳摄取会逐渐降低生长速率和乙酸盐排泄，直到防止乙酸盐排泄。对于其余四种碳源，摄取显然受到限制，产物是生物量、二氧化碳和水。与进入非磷酸化途径的碳源相比，为CMPs磷酸化部分提供碳源的碳源向前体（Pre - C）输送的碳相对更多，而不是输送到二氧化碳。前者的Pre - C/CO2比值为1.73 - 3.91，后者为0.46 - 0.78。对所有11种碳源的通量分析表明，在所有表型和条件下，直至μ为0.72的葡萄糖恒化器培养条件下，CMPs产生的“能量”（ATP + [2H]）供应过剩。这种多余的能量是一种热力学上的低效率，必须以热的形式耗散。大肠杆菌ML308可能是在“丰裕”和“匮乏”的环境中进化而来的。所选择的两种策略（多余碳的排泄和μ的限制）似乎是针对“丰裕”的防御机制。推测可能存在针对“匮乏”的防御机制。这些在通量分析中并不明显，但不可逆酶的变构控制会保护必需营养物质库在“匮乏”突然出现时不被迅速耗尽。
