Elucidation of salicylate attachment in celesticetin biosynthesis opens the door to create a library of more efficient hybrid lincosamide antibiotics.

ABSTRACT: Lincosamides, which are produced by streptomycetes, compose a small but clinically important class of antibiotics. The recent elucidation of the condensation and post-condensation biosynthetic steps of the lincosamides lincomycin and celesticetin revealed several unexpected reaction mechanisms. Here, we prepared recombinant proteins involved in the celesticetin biosynthetic pathway and used them for in vitro assays that were monitored by LC-MS. Our results elucidate the last biosynthetic step of celesticetin: the attachment of salicylic acid is catalyzed by the Ccb2 acyl-CoA ligase and the Ccb1 acyltransferase. Ccb1 belongs to the WS/DGAT protein family and, in contrast to the characterized members of the family, has unusual substrate specificity. To the best of our knowledge, Ccb1

SUBMITTER: Kadlcik S 

PROVIDER: S-EPMC5416915 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature