Enhanced biosynthesis of 3,4-dihydroxybutyric acid by engineered Escherichia coli in a dual-substrate system

3,4-Dihydroxybutyric acid (3,4-DHBA), a versatile platform four carbon (C4) chemical, can be used as a precursor in the production of many commercially important chemicals. Here, a dual-substrate biosynthesis system was developed for 3,4-DHBA production via a synthetic pathway established in an engineered Escherichia coli, and using xylose as a synthetic substrate and glucose as a cell growth substrate. The deletion of genes xylA, yjhH and yagE and others encoding for alcohol dehydrogenases in E. coli is essential for the production of 3,4-DHBA. Blocking competing pathway by removing the gene yiaE encoding for a 2-keto-3-deoxy-D-xylonate reductase also facilitated carbon flow towards the synthesis of 3,4-DHBA. Furthermore, regulation the availability of NAD⁺ resulted in further improved 3,4-DHBA production. The combinational optimization of the biosynthesis system led to a production of 0.38g/L 3,4-DHBA. This study provides an alternative 3,4-DHBA biosynthesis approach with the possibility of utilizing hydrolysates of lignocellulosic biomass as substrates.