Biocatalytic synthesis of asymmetric water-soluble indirubin derivatives

A method for the synthesis of asymmetric carboxy-substituted indirubins is presented. It employs indole-5carboxylic acid or indole-6-carboxylic acid and 2-indolinone derivatives as substrates for bacterial monooxygenase-driven enzymatic bioconversion in different bacterial hosts. This bioconversion system achieved the highest titer of monocarboxyindirubin production of up to 327 mg L-1 for 5-bromoindirubin-6 & PRIME;-carboxylic acid during the 16-h incubation period. The purified monocarboxyindirubins exhibited high solubility in water, up to three orders of magnitude higher than that of indirubin. In addition, several monocarboxyindirubins, namely 1-methylindirubin-5 & PRIME;-carboxylic acid, possess potent antiproliferative activity against different cancer cell lines. Therefore, the synthesis method for monocarboxyindirubins described herein is an efficient and environmentally friendly bioconversion system and the synthesized monocarboxyindirubins show great promise due to their high water solubility and potential antiproliferative activity.

Automated summary

This article presents a method for synthesizing asymmetric carboxy-substituted indirubins. It uses indole-5-carboxylic acid or indole-6-carboxylic acid and 2-indolinone derivatives as substrates for bacterial monooxygenase-driven enzymatic bioconversion in different bacterial hosts. The bioconversion system achieved a high titer of monocarboxyindirubin production, with up to 327 mg/L for 5-bromoindirubin-6-carboxylic acid during a 16-hour incubation period. The synthesized monocarboxyindirubins have high water solubility and potential antiproliferative activity, making them promising candidates.