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Purpose Overproduction of desired metabolites usually sacrifices cell growth. Here we report that quorum sensing (QS) can be exploited to coordinate cell growth and lactic acid production in  Escherichia coli . Methods We engineered two QS strains: one strain overexpressing acyl-homoserine lactone (AHL) synthesis genes (“ON”), the other strain overexpressing both AHL synthesis and degradation gene ( aiiA ) (“ON to semi-OFF”). To clarify the impact of the QS system on lactic acid production, D-lactate dehydrogenase gene  ldhA  was deleted from the  E. coli  genome, and Enhanced Green Fluorescence Protein (eGFP) was used as the reporter. Results Compared to the “ON” strain, the “ON to semi-OFF” strain showed delayed log growth and decreased  egfp  expression at stationary phase. When  egfp  was replaced by  ldhA  for lactic acid production, compared to the wild-type strain, the “ON to semi-OFF” strain demonstrated 231.9% and 117.3% increase in D-lactic acid titer and space-time yield, respectively, while the “ON” strain demonstrated 83.6%, 31%, and 36% increase in growth rate, maximum OD 600 , and glucose consumption rate, respectively. Quantitative real-time PCR revealed that both  ldhA  and the genes for phosphotransferase system were up-regulated in  ldhA- overexpressing “ON” strain compared to the strain only harboring QS system. Moreover, the “ON” strain showed considerable increase in glucose consumption after a short lag phase. Compared to the reference strain harboring only  ldhA  gene in vector, both the “ON” and “ON to semi-OFF” strains demonstrated synchronization between cell growth and D-lactic acid production. Conclusions Collectively, QS can be leveraged to coordinate microbial growth and product formation.

Leveraging quorum sensing system for automatic coordination of Escherichia coli growth and lactic acid biosynthesis