A synthetic methylotroph achieves accelerated cell growth by alleviating transcription-replication conflicts.

ABSTRACT: Microbial utilization of methanol for valorization is an effective way to advance green bio-manufacturing technology. Although synthetic methylotrophs have been developed, strategies to enhance their cell growth rate and internal regulatory mechanism remain underexplored. In this study, we design a synthetic methanol assimilation (SMA) pathway containing only six enzymes linked to central carbon metabolism, which does not require energy and carbon emissions. Through rational design and laboratory evolution, E. coli harboring with the SMA pathway is converted into a synthetic methylotroph. By self-adjusting the expression of TOPAI (topoisomerase I inhibitor) to alleviate transcriptional-replication conflicts (TRCs), the doubling time of methylotrophic E. coli is reduced to 4.5 h, approachin

SUBMITTER: Meng X 

PROVIDER: S-EPMC11695965 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature