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High-Level Production of Lycopene

Technology Overview

The technology involves the development of an Escherichia coli-based modular system for the production of apocarotenoids. Apocarotenoids such as α-, β-ionone and retinol are known to have high commercial values in the cosmetic industry. The team has incorporated enzyme engineering approaches into modular metabolic engineering strategy (N-terminal truncation and protein fusion) which led to a significant increase in α-ionone production from 0.5 to 30mg/L in flasks and 480mg/L in fed-batch fermentation. The optimized apocarotenoid strain was successfully re-engineered to produce 30mg/L and 500mg/L of β-ionone in flask and bioreactor respectively (>80 fold higher than previously reported in the literature). Similarly, 33mg/L of retinoids was produced in the flask by the reconstructed apocarotenoid module, demonstrating the versatility of the “plug-n-play” modulator system. The study highlights the importance of the strategy of simultaneous modular pathway optimization and enzyme engineering to overproduce valuable chemicals in microbes.

Technology Features & Specifications

The optimized apocarotenoid strain was successfully re-engineered to produce 30mg/L and 500mg/L of β-ionone in flask and bioreactor respectively (>80 fold higher than previously reported in the literature). There's a significant increase in α-ionone production from 0.5 to 30mg/L in flasks and 480mg/L in fed-batch fermentation. Similarly, 33mg/L of retinoids was produced in the flask by the reconstructed apocarotenoid module, demonstrating the versatility of the “plug-n-play” modulator system.

Potential Applications

Sustainable production of high levels of α-ionone and β-ionone from renewable resources in the food nutrition and consumer care industry.

Market Trends and Opportunities

The recent changes in the regulation of natural ingredient labeling have resulted in the increase in demand for natural flavours and fragrances. Consequently, there are growing interests in engineering microbes to produce the ingredients from renewable resources. Particularly, many apocarotenoids are important aroma molecules. However, the complex metabolic characteristics of apocarotenoid pathway have hampered the development of highly efficient microbial processes. Here, modular metabolic engineering and enzyme engineering strategies were systematically applied to effectively minimize the metabolic burden imposed by overexpression of 13 enzymes and to overcome the challenge from critical enzymes of low activities. Together, the strategy enabled the development of a robust E. coli strain capable of producing unprecedented yields of α-ionone and β-ionone, demonstrating the great potential of using microbes in the production of natural flavours and fragrances.

Customer Benefits

Sustainable production of high levels of α-ionone and β-ionone from renewable resources. The optimized pathway can also lead to a plethora of other compounds of interest such as lycopene, phytoene, phytofluene etc.

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