Biosynthesis of an engineered tautomycetin analogue via disruption of tmcK-encoding terminal decarboxylase in Streptomyces CK4412

► TMC terminal decarboxylation is carried out by the TmcJ-assisted TmcK in Streptomyces CK4412. ► TMC terminal decarboxylation is one of the rate-limiting steps in TMC biosynthesis. ► C5-deoxy-3″-carboxylic TMC in Streptomyces CK4412 failed to show PP1 selectivity over PP2A. ► C5-deoxy-3″-carboxylic TMC in Streptomyces CK4412 exhibited reduced cytotoxicity. ► Modification of C3″ and/or C5 of TMC differentiates multiple biological activities.