Thiopeptides, or thiazolylpeptides, are a large family of highly modified peptide antibiotics that encompasses dozens of known metabolites. The biosynthetic origins for thiostrepton and other thiopeptides were recently revealed, and it is now well-established that these metabolites arise from the enzymatic tailoring of a linear, ribosomally-synthesized precursor peptide.  For thiostrepton, there are two key aspects of thiostrepton biosynthesis: (1) the processive posttranslational modification of the precursor peptide to construct the core thiopeptide macrocyclic scaffold and (2) the conversion of tryptophan to the quinaldic acid substituent that is later attached to the macrocycle.  The recent progress toward understanding the genetics and biochemistry facilitating the assembly of thiostrepton will be discussed in addition to our efforts in harnessing the posttranslational machinery for the production of variant thiostreptons by site-directed mutagenesis of the precursor peptide.

Thiostrepton biosynthesis and biosynthetic engineering

241st National Meeting (2011)

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