Developing a thermophilic cell factory for high-temperature production of 1,3-propanediol via host-mining and metabolic engineering

Because of the discovery of various thermophiles, high -tempera-ture fermentation is an emerging technology for efficient bio-manufacturing with decreased cooling cost and risk for contamina-tion. This study reveals a data-driven host-mining strategy for selecting thermophilic hosts that are desired for producing various target products by leveraging publicly available big data from genome sequencing. Using 1,3-propanediol (1,3-PDO) as a target product, a desired production host, Parageobacillus thermogluco-sidasius, was identified and engineered. The systematically con-structed strain was extensively modified to develop a preferable 1,3-PDO producer, and the engineered strain could produce 1,3-PDO with a titer of 5.9 g/L in flask fermentation at an extremely high temperature (60 degrees C). The bottleneck in glycerol metabolism in P. thermoglucosidasius was then analyzed using transcriptome analysis. This study enables microbial production of 1,3-PDO at the current highest fermentation temperature and demonstrates effectiveness and feasibility of our host-mining strategy for various products.