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Background  As bacteria-originated crude violacein, a natural indolocarbazole product, consists of violacein and deoxyviolacein, and can potentially be a new type of natural antibiotics, the reconstruction of an effective metabolic pathway for crude violacein (violacein and deoxyviolacein mixture) synthesis directly from glucose in  Escherichia coli  was of importance for developing industrial production process.    Results  Strains with a multivariate module for varied tryptophan productivities were firstly generated by combinatorial knockout of  trpR/tnaA/pheA  genes and overexpression of two key genes  trpE   fbr   /trpD  from the upstream tryptophan metabolic pathway. Then, the gene cluster of violacein biosynthetic pathway was introduced downstream of the generated tryptophan pathway. After combination of these two pathways, maximum crude violacein production directly from glucose by  E. coli  B2/pED + pVio was realized with a titer of 0.6 ± 0.01 g L −1  in flask culture, which was four fold higher than that of the control without the tryptophan pathway up-regulation. In a 5-L bioreactor batch fermentation with glucose as the carbon source, the recombinant  E. coli  B2/pED + pVio exhibited a crude violacein titer of 1.75 g L −1  and a productivity of 36 mg L −1  h −1 , which was the highest titer and productivity reported so far under the similar culture conditions without tryptophan addition.    Conclusion  Metabolic pathway analysis using  13 C labeling illustrated that the up-regulated tryptophan supply enhanced tryptophan metabolism from glucose, whereas the introduction of violacein pathway drew more carbon flux from glucose to tryptophan, thereby contributing to the effective production of crude violacein in the engineered  E. coli  cell factory.    Electronic supplementary material  The online version of this article (doi:10.1186/s12934-015-0192-x) contains supplementary material, which is available to authorized users.

microbial cell factories

High crude violacein production from glucose by Escherichia coli engineered with interactive control of tryptophan pathway and violacein biosynthetic pathway