caa a22 4500 606212760 CHVBK 20210128101044.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10295-015-1591-z doi (NATIONALLICENCE)springer-10.1007/s10295-015-1591-z Production of tyrosine through phenylalanine hydroxylation bypasses the intrinsic feedback inhibition in Escherichia coli [Elektronische Daten] [Jin Huang, Yuheng Lin, Qipeng Yuan, Yajun Yan] Tyrosine is a proteinogenic aromatic amino acid that is often used as a supplementof food and animal feed, as well as a (bio-)synthetic precursor to various pharmaceutically or industrially important molecules. Extensive metabolic engineering efforts have been made towards the efficient and cost-effective microbial production of tyrosine. Conventional strategies usually focus on eliminating intrinsic feedback inhibition and redirecting carbon flux into the shikimate pathway. In this study, we found that continuous conversion of phenylalanine into tyrosine by the action of tetrahydromonapterin (MH4)-utilizing phenylalanine 4-hydroxylase (P4H) can bypass the feedback inhibition in Escherichia coli, leading to tyrosine accumulation in the cultures. First, expression of the P4H from Xanthomonas campestris in combination with an MH4 recycling system in wild-type E. coli allowed the strain to accumulate tyrosine at 262mg/L. On this basis, enhanced expression of the key enzymes associated with the shikimate pathway and the MH4 biosynthetic pathway resulted in the elevation of tyrosine production up to 401mg/L in shake flasks. This work demonstrated a novel approach to tyrosine production and verified the possibility to alleviate feedback inhibition by creating a phenylalanine sink. Society for Industrial Microbiology and Biotechnology, 2015 Phenylalanine nationallicence Tyrosine nationallicence Phenylalanine 4-hydroxylase nationallicence Metabolic engineering nationallicence Huang Jin State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 100029, Beijing, China aut Lin Yuheng College of Engineering, University of Georgia, 30602, Athens, GA, USA aut Yuan Qipeng State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 100029, Beijing, China aut Yan Yajun BioChemical Engineering Program, College of Engineering, 601B Driftmier Engineering Center, University of Georgia, 30602, Athens, GA, USA aut Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/4(2015-04-01), 655-659 1367-5435 42:4<655 2015 42 10295 https://doi.org/10.1007/s10295-015-1591-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10295-015-1591-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Huang Jin State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 100029, Beijing, China aut NATIONALLICENCE 700 1- Lin Yuheng College of Engineering, University of Georgia, 30602, Athens, GA, USA aut NATIONALLICENCE 700 1- Yuan Qipeng State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 100029, Beijing, China aut NATIONALLICENCE 700 1- Yan Yajun BioChemical Engineering Program, College of Engineering, 601B Driftmier Engineering Center, University of Georgia, 30602, Athens, GA, USA aut NATIONALLICENCE 773 0- Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/4(2015-04-01), 655-659 1367-5435 42:4<655 2015 42 10295