文献类型：期刊文献

英文题名：Combinatorial strategies for production improvement of anti-tuberculosis antibiotics ilamycins E1/E2 from deep sea-derived Streptomyces atratus SCSIO ZH16 ΔilaR

作者：Zhu, Yunfei[1];Zheng, Gaofan[1];Xin, Xiujuan[1];Ma, Junying[2];Ju, Jianhua[2];An, Faliang[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, CAS Key Lab Tropi Cal Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, RNAM,Ctr Marine Microbiol,South China Sea Inst Oc, Guangzhou, Peoples R China

年份：2022

卷号：9

期号：1

外文期刊名：BIORESOURCES AND BIOPROCESSING

收录：;EI(收录号：20224413021860);WOS:【SCI-EXPANDED(收录号:WOS:000871191200001)】；

基金：This work was funded by the National Key R&D Program of China (Nos. 2019YFC0312504), and the National Natural Science Foundation of China (Nos. 41876189). This work was also supported by the Open Research Fund Program of State Key Laboratory of Bioreactor Engineering and Institute of Regulatory Science.

语种：英文

外文关键词：Ilamycins; Streptomyces atratus; Fermentation optimization; Exogenous adding strategy

摘要：Ilamycins E-1/E-2 are novel cyclic heptapeptides from Streptomyces atratus SCSIO ZH16, which have the MIC value of 9.8 nM against Mycobacterium tuberculosis H37Rv. However, the lower fermentative titer of ilamycins E-1/E-2 cut off further development for novel anti-TB lead drugs. In order to break the obstacle, the combinatorial strategy of medium optimization, fermentative parameters optimization, exogenous addition of metal ions, precursors, and surfactants was developed to promoted the production of ilamycins E-1/E-2. Addition of 1 mM ZnCl2 at 0 h, 1 g/L tyrosine at 96 h, and 2 g/L shikimic acid at 48 h increased the production of ilamycins E-1/E-2 from 13.51 to 762.50 +/- 23.15, 721.39 +/- 19.13, and 693.83 +/- 16.86 mg/L, respectively. qRT-PCR results showed that the transcription levels of key genes in Embden-Meyerhof-Parnas pathway, hexose phosphate shunt pathway, and shikimic acid pathway were upregulated. In addition, the production of ilamycins E-1/E-2 reached 790.34 mg/L in a 5-L bioreactor by combinatorial strategy. Combinatorial strategies were used for improving ilamycins E-1/E-2 production in S. atratus Delta ilaR and provided a sufficient basis on further clinic development.