Systematical engineering of synthetic yeast for enhanced production of lycopene

Synthetic biology allows the re-engineering of biological systems and promotes the development of bioengineering to a whole new level, showing great potentials in bio-manufacture. Here, in order to make the heterologous pathway compatible with the chassis, we evolved the strain with a unique Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system which is built in the synthetic chromosome. By inducing SCRaMbLE, we successfully identified a chassis strain that can maintain the high yield while the rearranged chromosome content and introduced heterologous pathway show minimal effect on the yeast cell physiology. Then in the SCRaMbLEd strains we integrated the lycopene biosynthesis pathway into rDNA array to further increase its copy number and optimized the culturing condition, which lead to a 55.7-times increase of lycopene yield in the final yeast strain comparing to its parental strain. Our work potentially shows that by combining the engineering efforts on both natural product biosynthesis pathway and its host strain can further promote the potential of engineered host strain that is also high compatible to its heterologous over-expressed pathway of target product.