文献类型：期刊文献

英文题名：Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S-erythraea E3 and NRRL23338 strains

作者：Li, Yuan-Yuan[1];Chang, Xiao[1,3,5];Yu, Wen-Bang[2];Li, Hao[2];Ye, Zhi-Qiang[1,4];Yu, Hui[1,3];Liu, Bao-Hong[1];Zhang, Yan[2];Zhang, Si-Liang[2];Ye, Bang-Ce[1,2];Li, Yi-Xue[1,3]

机构：[1]Shanghai Ctr Bioinformat Technol, Shanghai 201203, Peoples R China;[2]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biol Sci, Bioinformat Ctr, Key Lab Syst Biol, Shanghai 200031, Peoples R China;[4]Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen 518055, Peoples R China;[5]Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA

年份：2013

卷号：14

外文期刊名：BMC GENOMICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000322585200002)】；

基金：This work was financially supported by grants from National key basic research program (2012CB316501), National Key Technologies R&D Program (2012AA022101), National Natural Science Foundation of China (31171268, 31000380, and 21276079), and SRFDP (No. 20120074110009).

语种：英文

外文关键词：S. erythraea; Erythromycin biosynthesis; Functional comparative genetics; Regulation mechanism

摘要：Background: S. erythraea is a Gram-positive filamentous bacterium used for the industrial-scale production of erythromycin A which is of high clinical importance. In this work, we sequenced the whole genome of a high-producing strain (E3) obtained by random mutagenesis and screening from the wild-type strain NRRL23338, and examined time-series expression profiles of both E3 and NRRL23338. Based on the genomic data and transcriptpmic data of these two strains, we carried out comparative analysis of high-producing strain and wild-type strain at both the genomic level and the transcriptomic level. Results: We observed a large number of genetic variants including 60 insertions, 46 deletions and 584 single nucleotide variations (SNV) in E3 in comparison with NRRL23338, and the analysis of time series transcriptomic data indicated that the genes involved in erythromycin biosynthesis and feeder pathways were significantly up-regulated during the 60 hours time-course. According to our data, BldD, a previously identified ery cluster regulator, did not show any positive correlations with the expression of ery cluster, suggesting the existence of alternative regulation mechanisms of erythromycin synthesis in S. erythraea. Several potential regulators were then proposed by integration analysis of genomic and transcriptomic data. Conclusion: This is a demonstration of the functional comparative genomics between an industrial S. erythraea strain and the wild-type strain. These findings help to understand the global regulation mechanisms of erythromycin biosynthesis in S. erythraea, providing useful clues for genetic and metabolic engineering in the future.