Corrigendum to “Identification and characterization of wblA-dependent tmcT regulation during tautomycetin biosynthesis in Streptomyces sp. CK4412” [Biotechnol. Adv. 30 (2012) 202–209]

Abstract

Tautomycetin (TMC) is an unusual linear polyketide compound esterified with a cyclic anhydride. It exhibitsnovel activated T cell-specific immunosuppressant as well as anti-cancer activities. Previously, we isolatedand characterized the entire TMC biosynthetic gene cluster fromStreptomycessp. CK4412, including a TMCpathway-specific gene,tmcN, the over-expression of which led to a significant increase in TMC productivity. Inaddition, we also reported that WblA acts as a global down-regulator of antibiotic biosynthesis throughpathway-specific regulation inStreptomycesspecies. Here, we confirm that TmcT acts as another TMCpathway-specific regulator within the TMC biosynthetic cluster. Specifically,tmcTdeletion resulted in thecomplete loss of TMC production, whereas complementation with atmcT-carrying integrative plasmidsignificantly restored TMC biosynthesis. We also identified a 0.39 kbwblAortholog (namedwblAtmc) fromStreptomycessp. CK4412viagenomic DNA library screening that showed 96% amino acid identity compared toa previously-knownS. coelicolor wblA. Targeted gene disruption ofwblAtmcinStreptomycessp. CK4412exhibited approximately 3-fold higher TMC productivity than that in the wild-type strain. Moreover,transcription analyses of the TMC biosynthetic and regulatory genes revealed that the expression oftmcTwasstrongly down-regulated bywblAtmc. These results imply that the TMC biosynthetic regulation network iscontrolled by two pathway-specific positive regulator, WblAtmc-dependent TmcT as well as WblAtmc-independent TmcN inStreptomycessp. CK4412.