基于比速率及代谢流的黑曲霉突变株和野生株分析

黑曲霉具备优异的外源蛋白表达和分泌能力，从而被广泛应用于工业酶制剂的生产。通过研究黑曲霉突变株和野生株在相同培养条件下生理参数和代谢流的差异，确定了黑曲霉合成糖化酶过程中的限制性因素。宏观动力学分析发现，较之野生株，突变株具有较高的最大比生长速率，并且副产物得率降低了90%，底物利用率提高了近30%，表明突变株与野生株在碳源分配和产物转化率上具有明显的差异。利用流平衡分析（FBA）计算胞内代谢通量分布，发现还原力和核糖的供应水平是限制菌体合成的主要因素，而前体氨基酸是合成糖化酶最主要的限制性因素。这些研究结果为后续发酵工艺优化和菌株基因改造提供了有益的思路。

Comparison of Two Aspergillus niger Mutant and Wild Strains Based on q-rate and Flux Balance Analysis

Aspergillus niger is widely used in industrial enzyme production for its excellent protein expression and secretion capacity. The differences of physiological behaviors and metabolic flux distribution between Aspergillus niger mutant and wild strains under same cultivation conditions are investigated, so as to determine limited factors in glucoamylase production. Based on kinetic analysis, it is confirmed that the mutant strain gets a higher maximum specific growth rate (+30%), a lower by-product productivity (－90%) and a higher substrate uptake efficiency (+30%), which implies significant differences in carbon distribution and substrate usage efficiency between these two strains. By applying Flux Balance Analysis (FBA), it is found that supplies of reducing power and ribose are main factors which effect cell growth. What's more, precursor amino acids is confirmed to be the main limited factor in glucoamylase production. These conclusions provide significances for subsequent bioprocess optimization and strain gene modification.