caa a22 4500 605499365 CHVBK 20210128100550.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6718-7 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6718-7 Improving heterologous polyketide production in Escherichia coli by transporter engineering [Elektronische Daten] [Jingya Yang, Zhi-Qiang Xiong, Shu-Jie Song, Jian-Feng Wang, Hua-Jun Lv, Yong Wang] 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. Springer-Verlag Berlin Heidelberg, 2015 Efflux pump nationallicence Polyketide erythromycin nationallicence Escherichia coli nationallicence Heterologous production nationallicence Transcriptional regulator nationallicence Yang Jingya Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China aut Xiong Zhi-Qiang Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut Song Shu-Jie Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China aut Wang Jian-Feng Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut Lv Hua-Jun Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut Wang Yong Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8691-8700 0175-7598 99:20<8691 2015 99 253 https://doi.org/10.1007/s00253-015-6718-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6718-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Jingya Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China aut NATIONALLICENCE 700 1- Xiong Zhi-Qiang Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 700 1- Song Shu-Jie Food Science and Engineering, College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China aut NATIONALLICENCE 700 1- Wang Jian-Feng Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 700 1- Lv Hua-Jun Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 700 1- Wang Yong Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8691-8700 0175-7598 99:20<8691 2015 99 253