Improving heterologous polyketide production in Escherichia coli by transporter engineering

Verfasser / Beitragende:
[Jingya Yang, Zhi-Qiang Xiong, Shu-Jie Song, Jian-Feng Wang, Hua-Jun Lv, Yong Wang]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/20(2015-10-01), 8691-8700
Format:
Artikel (online)
ID: 605499365
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024 7 0 |a 10.1007/s00253-015-6718-7  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6718-7 
245 0 0 |a Improving heterologous polyketide production in Escherichia coli by transporter engineering  |h [Elektronische Daten]  |c [Jingya Yang, Zhi-Qiang Xiong, Shu-Jie Song, Jian-Feng Wang, Hua-Jun Lv, Yong Wang] 
520 3 |a Expelling heterologous compounds out of hosts by transporters is a potential strategy to enhance product titers in microbial cell factories. In this work, to increase heterologous polyketide 6-deoxyerythronolide B (6dEB, erythromycin precursor) production, tripartite multidrug efflux pumps MacAB-TolC, AcrAB-TolC, MdtEF-TolC, and MexAB-OprM were modulated in a 6dEB production strain. Compared with the control, overexpression of a single component of efflux pumps (except oprM) repressed 6dEB production, but modulation of two components MacA and MacB or the complete pumps MacAB-TolC and MdtEF-TolC significantly improved 6dEB titer by 100±11, 118±54, and 98±12%, respectively. In addition, to avoid the challenging fine-tuning components of pumps, the transcriptional regulators of efflux pumps were modulated to improve the 6dEB production. Overexpression of RpoH (activator of MdtEF-TolC) and EvgA (activator of EmrKY-TolC and AcrAD-TolC) strongly increased 6dEB titer by 152±54 and 142±85%, respectively. This is the first report of transporter engineering for improving heterologous polyketide production in Escherichia coli. Our results provide an effective strategy for improving the yield of the heterologous products in chassis cell. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Efflux pump  |2 nationallicence 
690 7 |a Polyketide erythromycin  |2 nationallicence 
690 7 |a Escherichia coli  |2 nationallicence 
690 7 |a Heterologous production  |2 nationallicence 
690 7 |a Transcriptional regulator  |2 nationallicence 
700 1 |a Yang  |D Jingya  |u Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China  |4 aut 
700 1 |a Xiong  |D Zhi-Qiang  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
700 1 |a Song  |D Shu-Jie  |u Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China  |4 aut 
700 1 |a Wang  |D Jian-Feng  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
700 1 |a Lv  |D Hua-Jun  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
700 1 |a Wang  |D Yong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8691-8700  |x 0175-7598  |q 99:20<8691  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6718-7  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6718-7  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yang  |D Jingya  |u Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Xiong  |D Zhi-Qiang  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Song  |D Shu-Jie  |u Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Jian-Feng  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lv  |D Hua-Jun  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Yong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8691-8700  |x 0175-7598  |q 99:20<8691  |1 2015  |2 99  |o 253