Efficient production of cembratriene-ol in Escherichia coli via systematic optimization

Background The tobacco leaf–derived cembratriene-ol exhibits anti-insect effects, but its content in plants is scarce. Cembratriene-ol is difficult and inefficiently chemically synthesised due to its complex structure. Moreover, the titer of reported recombinant hosts producing cembratriene-ol was low and cannot be applied to industrial production. Results In this study, Pantoea ananatis geranylgeranyl diphosphate synthase (CrtE) and Nicotiana tabacum cembratriene-ol synthase (CBTS) were heterologously expressed to synthsize the cembratriene-ol in Escherichia coli . Overexpression of cbts* , the 1-deoxy- d -xylulose 5-phosphate synthase gene dxs , and isopentenyl diphosphate isomerase gene idi promoted the production of cembratriene-ol. The cembratriene-ol titer was 1.53-folds higher than that of E . coli Z17 due to the systematic regulation of ggpps , cbts* , dxs , and idi expression. The production of cembratriene-ol was boosted via the overexpression of genes ispA , ispD , and ispF . The production level of cembratriene-ol in the optimal medium at 72 h was 8.55-folds higher than that before fermentation optimisation. The cembratriene-ol titer in the 15-L fermenter reached 371.2 mg L − 1 , which was the highest titer reported. Conclusion In this study, the production of cembratriene-ol in E . coli was significantly enhanced via systematic optimization. It was suggested that the recombinant E . coli producing cembratriene-ol constructed in this study has potential for industrial production and applications.