Targeted engineering and scale up of lycopene overproduction in Escherichia coli

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Engineering microorganisms for production of terpenoids has attracted considerable attention, and initial success was achieved using traditional metabolic engineering strategies or high throughput screening methods. Recently, we used a new targeted engineering strategy to leverage the mevalonate pathway to overproduce farnesene, but it was not clear if this strategy is applicable to production of other terpenoids. Here, we directly extend the information to lycopene production. Only two mutants were constructed, and the titer of lycopene in strain L3 easily reached 1.44g/L in 2.5L fed-batch fermentation. When the scale was increased to a 100L working volume fed-batch fermentation in 150L fermenter, up to 1.23g/L (34.3mg/gDCW) of lycopene was produced at 32h after induction, the maximum productivity of this process reached up to 74.5mg/L/h which demonstrates that the L3 fermentation process is easy scalable and that L3 could potentially replace the natural producer Blakeslea trispora in industrial production. The information could also be used to develop a highly efficient platform for overproduction of other terpenoids.