BackgroundMicrobial production of lycopene, a commercially and medically important compound, has received increasing concern in recent years. Saccharomyces cerevisiae is regarded as a safer host for lycopene production than Escherichia coli. However, to date, the lycopene yield (mg/g DCW) in S. cerevisiae was lower than that in E. coli and did not facilitate downstream extraction process, which might be attributed to the incompatibility between host cell and heterologous pathway. Therefore, to achieve lycopene overproduction in S. cerevisiae, both host cell and heterologous pathway should be delicately engineered.ResultsIn this study, lycopene biosynthesis pathway was constructed by integration of CrtE, CrtB and CrtI in S. cerevisiae CEN.PK2. When YPL062W, a distant genetic locus, was deleted, little acetate was accumulated and approximately 100 % increase in cytosolic acetyl-CoA pool was achieved relative to that in parental strain. Through screening CrtE, CrtB and CrtI from diverse species, an optimal carotenogenic enzyme combination was obtained, and CrtI from Blakeslea trispora (BtCrtI) was found to have excellent performance on lycopene production as well as lycopene proportion in carotenoid. Then, the expression level of BtCrtI was fine-tuned and the effect of cell mating types was also evaluated. Finally, potential distant genetic targets (YJL064W, ROX1, and DOS2) were deleted and a stress-responsive transcription factor INO2 was also up-regulated. Through the above modifications between host cell and carotenogenic pathway, lycopene yield was increased by approximately 22-fold (from 2.43 to 54.63 mg/g DCW). Eventually, in fed-batch fermentation, lycopene production reached 55.56 mg/g DCW, which is the highest reported yield in yeasts.ConclusionsSaccharomyces cerevisiae was engineered to produce lycopene in this study. Through combining host engineering (distant genetic loci and cell mating types) with pathway engineering (enzyme screening and gene fine-tuning), lycopene yield was stepwise improved by 22-fold as compared to the starting strain. The highest lycopene yield (55.56 mg/g DCW) in yeasts was achieved in 5-L bioreactors. This study provides a good reference of combinatorial engineering of host cell and heterologous pathway for microbial overproduction of pharmaceutical and chemical products.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0509-4) contains supplementary material, which is available to authorized users.

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Fractional Chern insulators (FCIs), having properties similar to those of the fractional quantum Hall effect, have been established numerically in various toy models. To fully explore their fundamental physics and to develop practical applications, material realization is indispensable. Here we theoretically predict a realization of FCI in a two-dimensional organometallic material, which is known to have the prerequisite topological flat bands. Using numerical exact diagonalization we demonstrate that the presence of strong electronic correlations and fractional filling of such a system could lead to a rich phase diagram, including Abelian fractional quantum Hall (FQH), Fermi-liquid, and Wigner crystal states. In particular, the FQH state has been confirmed systematically by calculating the topological ground-state degeneracies, topological Chern number, and the quasihole excitation spectrum as well as the particle entanglement spectrum. Future experimental realization of the FQH state in such material may provide a route for developing practical applications of FCI with no need of the extreme conditions.