Transcriptomics-guided optimization of vitamins to enhance erythromycin yield in saccharopolyspora erythraea  

作　　者：Xiang Ke Xing Jiang Shuohan Wang Xiwei Tian Ju Chu 

机构地区：[1]State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,130 Meilong Road,Shanghai 200237,China [2]Qingdao Innovation Institute of East China University of Science and Technology,596-1 East Jiushui Road,Qingdao 266102,China

出　　处：《Bioresources and Bioprocessing》2024年第1期1366-1377,共12页生物资源与生物加工(英文)

基　　金：financially supported by the National Key Research Development Program of China(2022YFC2105403);the Taishan Scholars Program,the Shanghai Pilot Program for Basic Research(22TQ1400100-14);the Natural Science Foundation of Shanghai(23ZR1416500);the Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVJ1231036).

摘　　要：Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3,as compared to the wild-type NRRL 2338.An in-depth analysis was conducted on the effects of nine vitamins,and it was determined that thiamine pyrophosphate(TPP),vitamin B2,vitamin B6,vitamin B9,vitamin B12,and hemin are key enhancers in erythromycin production in E3,increasing the erythromycin titer by 7.96-12.66%.Then,the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency,enhancing the erythromycin titer in shake flasks by 39.2%.Otherwise,targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis.This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways,thereby boosting erythromycin production,and provides valuable directions for application on an industrial scale.

关 键 词：ERYTHROMYCIN VITAMIN Saccharopolyspora erythraea TRANSCRIPTOMICS Metabolomics Metabolic flux analysis 

分 类 号：R96[医药卫生—药理学]