Abstract: To solve the problem that the glucose consumption capacity of Corynebacterium glutamate differed at different stages of L-isoleucine production, the feeding rate of glucose was dynamically adjusted. Corynebacterium glutamate YILM1504 was cultured at an initial glucose concentration of 80 g/L and with suboptimal glucose feeding at a feeding rate equal to 90% of the maximum feeding rate. The dynamic glucose feeding rate was as follows: 0 g/(L·h) for 0–8 h, 5.40–7.47 g/(L·h) for 8–14 h, 7.47–7.00 g/(L·h) for 16–24 h, and 7.00–5.20 g/(L·h) for 24–40 h. The yield of L-isoleucine was 44.32 g/L and the conversion rate of glucose to L-isoleucine was 19.63%. The comparative analysis of metabolic flows revealed that the ratio of carbon distribution between and the hexose monophosphate pathway (HMP) and the Embden-Meyerhof-Parnas pathway (EMP) was 0.56. Moreover, the metabolic flow toward Ile was increased by 18.92%, while the metabolic flows toward Val, Leu, and Ala were reduced by 67.12%, 72.21%, and 30.23%. In conclusion, this fine glucose feeding strategy can meet the dynamic glucose demand of C. glutamicum during the fermentation process, resulting in enhanced isoleucine titer, reduced by-product accumulation and significantly prolonged acid production peak period.

Key words: L-isoleucine; suboptimal glucose addition; Corynebacterium glutamicum; metabolic flow