Production of natural indirubin from indican using non-recombinant Escherichia coli

► We show that non-recombinant E. coli is able to produce indirubin from indican. ► The yield is reliably determined to be about 25-35%. ► Further increase in yield (1.8-2.1 folds) is achieved by re-adding whole cells. ► This process is more effective than the typical process using indole as a substrate.