Systems metabolic engineering of Escherichia coli for the high-level production of deoxyviolacein, a natural colorant

Deoxyviolacein is a natural colorant with various biological properties, widely applied in cosmetic and pharmaceutical fields. However, current methods of deoxyviolacein production by natural producers may cause highly lethal infections in humans, limiting the sustainable production of deoxyviolacein. Here, an l-tryptophan-producing Escherichia coli strain was engineered for efficient deoxyviolacein production. First, the deoxyviolacein synthesis pathway was introduced and optimized to construct a base strain. Second, multi-modular engineering was conducted for further optimization, including engineering of the glucose uptake system and central metabolism and enhancement of precursor supply. To coordinate metabolic flux distribution, the optimal expression of aroG^Q151F, ppsA and tktA was tuned by generating libraries of tunable intergenic regions coupled with a novel l-tryptophan biosensor. Finally, the best-performing strain successfully accumulated 12.18 g/L of deoxyviolacein from glucose, showing a competitive deoxyviolacein titer reported to date and providing a paradigm for the production of value-added aromatic compounds in E. coli.