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Engineering Escherichia coli lifespan for enhancing chemical production


Industrial chemical production from renewable feedstocks by microbial cell factories provides a promising avenue towards sustainability. However, the small size of bacterial cells and environmental stress significantly affect microbial cell factory performance. Here, we engineered the Escherichia coli lifespan to improve the chemical production of poly(lactate-co-3-hydroxybutyrate) and butyrate. The replicative lifespan was shortened by deleting a carbon storage regulator, and the chronological lifespan was extended by deleting a response regulator and overexpressing sigma-38 in Escherichia coli. The replicative lifespan was fine-tuned using a two-output recombinase-based state machine, and the cell size was enlarged 13.4-fold. The highest poly(lactate-co-3-hydroxybutyrate) content of 52 wt% was achieved in a 5-l fermenter. The chronological lifespan was modulated through a multi-output recombinase-based state machine, resulting in the highest butyrate titre of 29.8 g l−1, by programming cell differentiation according to different fermentation stages. These results highlight the applicability of engineering the bacterial lifespan to increase microbial cell factory performance.

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Fig. 1: Characterization of CLS regulation by genetic manipulation.
Fig. 2: Characterization of RLS regulation by genetic manipulation.
Fig. 3: Overview of the design and validation of the TRSM.
Fig. 4: Overview of engineering RLS for PLH production.
Fig. 5: Overview of the design and validation of the MRSM.
Fig. 6: Overview of engineering CLS for butyrate production.

Data availability

The data that support the figures within this paper and other findings of this study are available from the corresponding author upon reasonable request. Supplementary Table 9 provides a list of the GenBank accession numbers of the 14 key plasmids constructed in this study.


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This work was supported by the National Key R&D Program of China (2018YFA0901401), the National Natural Science Foundation of China (21808083, 21878126), the Key Field R & D Program of Guangdong Province (2019B020218001) and the National First-Class Discipline Program of Light Industry Technology and Engineering (LITE2018-08).

Author information




L.G. and L.L. designed the project. L.G. and W.D. conducted and analysed the experiments. C.G., G.H., Q.D. and X.C. provided technical assistance. L.G. analysed the data and wrote the manuscript with input from C.Y., J.L. and L.L. All authors reviewed and approved the manuscript.

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Correspondence to Liming Liu.

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Guo, L., Diao, W., Gao, C. et al. Engineering Escherichia coli lifespan for enhancing chemical production. Nat Catal 3, 307–318 (2020).

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