title: Enhanced lycopene productivity by manipulation of carbon flow to isopentenyl diphosphate in Escherichia coli.
abstract: Lycopene is a useful phytochemical that holds great commercial value. In our study the lycopene production pathway in E. coli originating from the precursor isopentenyl diphosphate (IPP) of the non-mevalonate pathway was reconstructed. This engineered strain of E. coli accumulated lycopene intracellularly under aerobic conditions. As a next step, the production of lycopene was enhanced through metabolic engineering methodologies. Various competing pathways at the pyruvate and acetyl-CoA nodes were inactivated to divert more carbon flux to IPP and subsequently to lycopene. It was found that the ackA-pta, nuo mutant produced a higher amount of lycopene compared to the parent strain. To further enhance lycopene production, a novel mevalonate pathway, in addition to the already existing non-mevalonate pathway, was engineered. This pathway utilizes acetyl-CoA as precursor, condensing it to form acetoacetyl-CoA and subsequently leading to formation of IPP. Upon the introduction of this new pathway, lycopene production increased by over 2-fold compared to the ackA-pta, nuo mutant strain.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas 77005, USA.
authors.forename: Ravishankar V
authors.initials: RV
authors.lastname: Vadali
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Fu
authors.forename: George N
authors.initials: GN
authors.lastname: Bennett
authors.forename: Ka-Yiu
authors.initials: KY
authors.lastname: San
mesh_terms: D002244:Carbon / Q000378:metabolism*; D002338:Carotenoids / Q000096:biosynthesis*; D018929:Cell Culture Techniques / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D024861:Genetic Enhancement / Q000379:methods*; D045782:Hemiterpenes / Q000378:metabolism*; D000077276:Lycopene; D009943:Organophosphorus Compounds / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; C004809:isopentenyl pyrophosphate; D002338:Carotenoids; D002244:Carbon; D000077276:Lycopene