文献类型：期刊文献

英文题名：Controlling the feed rate of glucose and propanol for the enhancement of erythromycin production and exploration of propanol metabolism fate by quantitative metabolic flux analysis

作者：Chen, Yong[1,2];Huang, Mingzhi[1];Wang, Zejian[1];Chu, Ju[1];Zhuang, Yingping[1];Zhang, Siliang[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Qingdao Agr Univ, Food Sci & Engn Coll, Qingdao 266109, Shandong, Peoples R China

年份：2013

卷号：36

期号：10

起止页码：1445

外文期刊名：BIOPROCESS AND BIOSYSTEMS ENGINEERING

收录：;EI(收录号：20134016795973);WOS:【SCI-EXPANDED(收录号:WOS:000324214400012)】；

基金：This work was financially supported by a grant from the Major State Basic Research Development Program of China (973 Program, No. 2012CB721006), National Natural Science Foundation of China (No. 21276081), the National Scientific and Technological Major Special Project (Significant Creation of New drugs, No. 2011ZX09203-001-03), and Research Fund for the Doctoral Program of Higher Education of China (No. 20110074110015).

语种：英文

外文关键词：Erythromycin; Propanol; Metabolic flux analysis; Feeding strategy

摘要：In this paper, several different fermentation experiments were designed to address whether modulating glucose and propanol feeds could benefit the production level of erythromycin during pilot plant (30 L) fermentation. Results showed that glucose feed rate (determined by a set high or low culture pH) had no effect on erythromycin production, indicating that glucose was not the limiting factor for erythromycin biosynthesis under these conditions. It was found that decreasing glucose feed could stimulate the consumption of propanol, and the high erythromycin production (12.49 +/- A 0.50 mg ml(-1)) was achieved by controlling the feed rates of glucose and propanol. The quantitative metabolic flux analysis disclosed that high propanol consumption increased the pool size of propionyl-CoA (similar to 2.147 mmol g(-1) day(-1)) and methylmalonyl-CoA (similar to 1.708 mmolg(-1) day(-1)). It was also found that 45-77 % of the propanol went into the TCA cycle which strengthened the conclusion that blocking the propionate pathway to TCA cycle could lead to a significant increase in erythromycin production in carbohydrate-based media (Reeves et al. Ind Microbiol Biotechnol 7:600-609, 2006). In addition, the results also suggested that a relative low intracellular ATP level resulting from low glucose feed did not limit the erythromycin biosynthesis, and a relatively high NADPH should be beneficial for erythromycin biosynthesis.