Enhanced Lycopene Productivity by Manipulation of Carbon Flow to Isopentenyl Diphosphate in Escherichia coli

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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.