Abstract

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.

Highlights

  • Lycopene, a member of the carotenoid family [1], is widely used in food, pharmaceutical, and cosmetic industries because of its potent anti-cancer [2], anti-inflammatory [3], and anti-oxidative activities [4]

  • We summarized the recent advances in lycopene production by the engineered E. coli using metabolic engineering strategies

  • The one in eukaryotes involves two reactions successively catalyzed by MVAP kinase (PMK) and MVAPP decarboxylase (MDD), while the other pathway in archaea harbors two reactions catalyzed by MVAP decarboxylase (MPD) and isopentenyl phosphate kinase (IPK), respectively [26]

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Summary

Introduction

A member of the carotenoid family [1], is widely used in food, pharmaceutical, and cosmetic industries because of its potent anti-cancer [2], anti-inflammatory [3], and anti-oxidative activities [4]. Lycopene production by chemical synthesis is high-cost, low-yielding, and environmentally unfriendly [10]. The native MEP pathway present in E. coli facilitates the production of terpenoids including lycopene. This pathway showed low metabolite flux in metabolic engineering [23], leading to the introduction of the heterogeneous MVA pathway into E. coli for lycopene production. We summarized the recent advances in lycopene production by the engineered E. coli using metabolic engineering strategies. Current investigations on the modification of the two metabolic pathways, MEP and MVA, for lycopene production in E. coli, were reviewed. 2. Metabolic Engineering of Two Major Pathways in E. coli for Lycopene Production

The Primary Biosynthetic Pathways for Lycopene Production
Metabolic Engineering of the Heterogeneous MVA Pathway
Optimization of Other Metabolic Pathways to Enhance Lycopene Production
Diagram
Engineering Regulatory Networks to Enhance Lycopene Production
Optimization of Auxiliary
Other Engineering Strategies for Lycopene Production
Findings
Discussion and Future
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