Establishment of an efficient expression and regulation system in Streptomyces for economical and high-level production of the natural blue pigment indigoidine

Abstract

Abstract Background Indigoidine, as a kind of natural blue pigment, is widely used in textiles, food, and pharmaceutical and mainly synthesized from L-glutamine via a condensation reaction by indigoidine synthetases, most of which originated from Streptomyces species. Although Streptomyces possesses strong secondary metabolism, the switches of which from the primary metabolism are complex and thus a challenge to holistically optimize their productivities. Therefore, most of the researchers choose to over-express indigoidine synthetases in the heterologous host to achieve high-level production of indigoidine. Results Considering the advantages of low-cost culture medium and simple culture conditions during the large-scale culture of Streptomyces, here, an updated regulation system derived from Streptomyces self-sustaining system, constructed in our previous study, was established for the highly efficient production of indigoidine in Streptomyces lividans TK24. The updated system was constructed via promoter mining and σhrdB expression optimization, and this system was applied to precisely and continuously regulate the expression of indigoidine synthetase IndC derived from Streptomyces albus J1704. Finally, the engineered strain was cultured in the cheap industrial medium, and 14.3 g/L and 46.27 g/L indigoidine could be achieved in flask and 4 L fermentor, respectively, reaching the highest level of microbial synthesis of indigoidine. Conclusions This study will lay a foundation for the industrial application of Streptomyces cell factories to produce indigoidine.