Carotenoids production in metabolically engineered Escherichia coli

Abstract

Carotenoids are important organic pigments that have been widely used in food, animal feed, cosmetics, and health industries. Plants and alga have been major sources of many different natural carotenoids. However, they are affected by weather and environmental conditions and their successful extraction is rather limited. Chemical synthesis is inefficient due to the complexity of their chemical structures involving enantioselectivity and regioselectivity. For these reasons, an alternative means of overproducing valuable natural carotenoids using microorganisms has emerged. In this study, Escherichia coli, which can be rapidly grown to a high density and can be engineered with well-established genetic engineering tools was used as a chassis strain. First, E. coli strain producing astaxanthin was developed by systems metabolic engineering. After that, E. coli strain producing lutein was developed employing strategies including substrate channeling and electron channeling. The strategies used for lutein production were succefully applied on production of apigenin, which is categorized as flavonoid, confirming that the strategies can be generally utilized for microbial production of natural compounds. Next, to expand the membrane capacity to accumulate intracellularly produced carotenoids which are integrated into the cell membrane due to their hydrophobic propteries, various membrane engineering strategies were examined. Consequently, E. coli strains each producing $\beta$-carotene, zeaxanthin and astaxanthin in high amount were developed. The metabolic engineering strategies used here could be extensively applied to the microbial production of carotenoids and natural compounds.