title: Identification of novel knockout and up-regulated targets  for improving isoprenoid production in E. coli.
abstract: Discovery of novel potential genetic targets to increase the supply of isoprenoid precursors, isopentyl/dimethylallyl diphosphate, is of importance for microbial production of isoprenoids. Here, to improve isoprenoid precursor supply, a flux distribution comparison analysis, based on the genome-scale model, was utilized to simultaneously predict the knockout, down- and up-regulated targets in Escherichia coli. 51 targets were in silico discovered. All knockout and up-regulated targets were experimentally tested to enhance lycopene production. Five knockout targets (deoB, yhfw, yahI, pta and eutD) and four up-regulated targets (ompN, ompE, ndk and cmk) led to 10-45% increases of lycopene yield, respectively, which had not been uncovered in previous studies. When engineering of the five most significant targets gdhA, eutD, tpiA, ompE and ompN, were combined the lycopene titer improved by 174% in shake-flask and 81% in bioreactor fermentations with a maximum yield of 454 mg l(-1).
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Wang
authors.forename: Hai-lin
authors.initials: HL
authors.lastname: Meng
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Xiong
authors.forename: Si-liang
authors.initials: SL
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002338:Carotenoids / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D003198:Computer Simulation; D015536:Down-Regulation / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D055786:Gene Knockout Techniques; D005818:Genetic Engineering; D000077276:Lycopene; D008954:Models, Biological; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002338:Carotenoids; D000077276:Lycopene