(85d) Lycopene Production from Fatty Acids By Fed-Batch Fermentation of Metabolically Engineered Escherichia coli

Na Liu, Ya-Hue Valerie Soong, Dongming Xie*

Department of Chemical Engineering, Massachusetts Biomanufacturing Center, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.

Abstract

Lycopene has long been used as functional food, nutraceutical, pharmaceutical and cosmetic due to its anti-oxidation and anti-cancer activities. Microbial production of lycopene has attached more and more attention in recent years since it is more economical and sustainable as compared to traditional methods of making lycopene from chemical synthesis and extraction from tomatoes. Currently, research on microbial production has been focusing on using glucose as the substrate to synthesize lycopene by metabolic engineering. In this study, the Escherichia coli strain R122 was engineered to produce lycopene from hydrophilic substrates (glucose/glycerol) by introducing the MVA and lycopene synthesis pathways. The E. coli strain FA03-PM was generated by further introducing the fatty acid transport system so that it can produce lycopene form both hydrophilic substrate and fatty acids. Under 1-L fed-batch fermentation conditions, strain R122 produced 11 g/L DCW and 0.27 g/L lycopene from glucose with a specific titer 26 mg/g in biomass. Under similar fermentation conditions, the fatty acids utilization strain FA03-PM produced 31 g/L DCW and 1.4 g/L lycopene from oleic acid (C18:1) with a specific titer 45 mg/g in biomass. Though strain FA03-PM was designed for producing lycopene from fatty acid, the possible inefficient mixing and mass transfer of fatty acid in aqueous medium and the lack of optimization of the fatty acid metabolism pathway limited the strain’s capability for higher lycopene production from a specific fatty acid alone. It was found that FA03-PM produced significantly more lycopene with titers of 2.4~2.7 g/L and specific titers of 63-84 mg/g within 40~48 h when glucose was used as the sole substrate or mixed with oleic acid at a 1:1 carbon ratio. The achieved lycopene titer and the specific titer in biomass are also among the highest levels in all published results. Our research will also help further engineer strains and bioprocesses in future for biomanufacturing of high-value products from the common agriculture commodities, oils and fats.

Keywords: lycopene, metabolic engineering, fed-batch fermentation.