High production of lycopene from recombinant E. coli by using engineered non-coding RNAs

Isoprenoids including carotenoids are the most chemically diverse family of compounds found in nature. Carotenoids are synthesized from isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). There are two pathways of 2-C-Methyl-D-erythritol-4-phosphate (MEP) and mevalonate (MVA) for IPP synthesis. In order to increase building block synthesis in E. coli with MEP pathway, foreign MVA pathway is additionally introduced into the host chromosome, resulting into an whole MVA pathway integration strain named SBL1. Multiple-copies of lycopene biosynthesis operon are integrated into E. coli chromosomal sites corresponding to by-product production, resulting in final lycopene production strain named SBL7. The engineered SBL7 strain produced a significant amount of lycopene without formation of inhibitory by-product such as acetate, lactate, and ethanol. To further improve lycopene production, we introduced each of 99 non-coding RNAs (ncRNAs) into SBL7. As a result, we found that micA and IS128 are responsible for enhancement of lycopene production. This work was supported by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT & Future Planning (2011-0031964).