Metabolic Engineering Escherichia coli for the Production of Lycopene

Abstract

<jats:p>Lycopene, a potent antioxidant, has been widely used in the fields of pharmaceuticals, nutraceuticals, and cosmetics. However, the production of lycopene extracted from natural sources is far from meeting the demand. Consequently, synthetic biology and metabolic engineering have been employed to develop microbial cell factories for lycopene production. Due to the advantages of rapid growth, complete genetic background, and a reliable genetic operation technique, Escherichia coli has become the preferred host cell for microbial biochemicals production. In this review, the recent advances in biological lycopene production using engineered E. coli strains are summarized: First, modification of the endogenous MEP pathway and introduction of the heterogeneous MVA pathway for lycopene production are outlined. Second, the common challenges and strategies for lycopene biosynthesis are also presented, such as the optimization of other metabolic pathways, modulation of regulatory networks, and optimization of auxiliary carbon sources and the fermentation process. Finally, the future prospects for the improvement of lycopene biosynthesis are also discussed.</jats:p>

Plant-Derived Cell-Free Biofactories for the Production of Secondary Metabolites

“…The major commercial source of lycopene is currently tomato fruits, although the extraction of lycopene from plants is expensive and environmentally harmful. This has prompted the transfer of the metabolic pathway to microbial production platforms such as E. coli, Saccharomyces cerevisiae and Yarrowia lipolytica (Li et al, 2020;Wang et al, 2020). During the last year, the productivity of these engineered biofactories has been improved significantly, mainly by engineering gene expression, improving lycopene storage capacity, optimizing fermentation processes, and combinatorial pathway engineering (Li et al, 2020).…”

Engineering Vibrio sp. SP1 for the production of carotenoids directly from brown macroalgae

“…Nevertheless, additional development of this strain using various genetic tools is mandatory to further increase titer, yield, and productivity of value-added products for brown macroalgae-based biorefinery in the future. Previously, elevation in bottleneck enzyme expression [47] , heterologous expression of mevalonate (MVA) pathway which is absent in most bacteria [48] , and deletion of competing pathways were endeavored and proved to increase their titer in several folds [49] . Introducing such extensive modifications would become a lot more easier owing to recently developed natural competent system in Vibrio species [50] , [51] .…”

Systematical Engineering of Synthetic Yeast for Enhanced Production of Lycopene

“…As a plant derived nutrient with antioxidant properties, lycopene is commonly used as a food additive [ 1 ] and its biosynthesis pathway has been well-characterized [ 2 ]. Production of lycopene using microbial sources, such as Blakeslea trispora [ 3 , 4 ], Escherichia coli [ 5 , 6 , 7 , 8 , 9 ], and Saccharomyces cerevisiae [ 10 , 11 , 12 , 13 , 14 ], is presently of great interest. By random mutagenesis against B. trispora on its whole genome and fermentation optimization, the yield of lycopene has been increased up to 944.8 mg/L [ 3 ].…”

“…By random mutagenesis against B. trispora on its whole genome and fermentation optimization, the yield of lycopene has been increased up to 944.8 mg/L [ 3 ]. Since E. coli cannot produce lycopene naturally, extensive metabolic engineering efforts, such as whole pathway engineering, cofactor engineering, membrane engineering, and directed evolution have been conducted to reach the lycopene yield of 448 mg/g dry cell weight (DCW) [ 5 , 6 , 7 , 8 , 9 ]. However, microbial production of lycopene in B. trispora [ 15 ] or E. coli has its own shortcomings due to food safety issues [ 16 ].…”