Abstract
Synthetic biology allows the re-engineering of biological systems and promotes the development of bioengineering to a whole new level, showing great potential in biomanufacturing. Here, in order to make the heterologous lycopene biosynthesis pathway compatible with the host strain YSy 200, we evolved YSy200 using a unique Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system that is built in the Sc2.0 synthetic yeast. By inducing SCRaMbLE, we successfully identified a host strain YSy201 that can be served as a suitable host to maintain the heterologous lycopene biosynthesis pathway. Then, we optimized the lycopene biosynthesis pathway and further integrated into the rDNA arrays of YSy201 to increase its copy number. In combination with culturing condition optimization, we successfully screened out the final yeast strain YSy222, which showed a 129.5-fold increase of lycopene yield in comparison with its parental strain. Our work shows that, the strategy of combining the engineering efforts on both the lycopene biosynthesis pathway and the host strain can improve the compatibility between the heterologous pathway and the host strain, which can further effectively increase the yield of the target product.
Highlights
As a plant derived nutrient with antioxidant properties, lycopene is commonly used as a food additive [1] and its biosynthesis pathway has been well-characterized [2]
The highest lycopene yield up to date in Saccharomyces cerevisiae is achieved by extensive rational engineering efforts against multiple targeted genes
We successfully demonstrated how SCRaMbLE creates genetic variations to host the exogenous lycopene pathway, and omics analysis allow us to identify combinatorial factors that contribute to the lycopene production
Summary
As a plant derived nutrient with antioxidant properties, lycopene is commonly used as a food additive [1] and its biosynthesis pathway has been well-characterized [2]. Production of lycopene using microbial sources, such as Blakeslea trispora [3,4], Escherichia coli [5,6,7,8,9], and Saccharomyces cerevisiae [10,11,12,13,14], is presently of great interest. Microbial production of lycopene in B. trispora [15] or E. coli has its own shortcomings due to food. Bioengineering 2021, 8, 14 safety issues [16]. Engineering yeast, especially S. cerevisiae for increased lycopene production, have been investigated extensively [10,11,12,13,14]
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