title: Metabolic engineering of Escherichia coli to enhance shikimic acid production from sorbitol.
abstract: Shikimic acid (SA) is the key synthetic material of Oseltamivir, which is an effective drug for the prevention and treatment of influenza. In this study, to block the downstream metabolic pathway of SA, the shikimate kinase isoenzyme genes aroK and aroL were deleted by Red recombination. Moreover, the key enzyme genes aroG, aroB, tktA and aroE of SA pathway were co-expressed by constructing the recombinant vector pETDuet-GBAE. As a result, SA production of E. coli BW25113 (∆aroL/aroK, DE3)/pETDuet-GBAE reached 1,077.6 mg/l when low amounts of sorbitol (5 g/l) were fed in shake flasks. The yield was 3.7 times that when glucose was used (P < 0.05). The results showed that sorbitol was an optimized carbon source for the high efficient accumulation of SA for the first time, which was applicable to use in the industry for high yields and low consumption.
authors.affiliation: State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 200040, China.
authors.forename: Xianglei
authors.initials: X
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Haifeng
authors.initials: H
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Baoquan
authors.initials: B
authors.lastname: Zhu
mesh_terms: D002244:Carbon / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012765:Shikimic Acid / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D012765:Shikimic Acid; D013012:Sorbitol; D002244:Carbon