Authentic Heterologous Expression of the Tenellin Iterative Polyketide Synthase Nonribosomal Peptide Synthetase Requires Coexpression with an Enoyl Reductase

ChemBioChem
2008.0

Abstract

<jats:title>Abstract</jats:title><jats:p>The <jats:italic>tenS</jats:italic> gene encoding tenellin synthetase (TENS), a 4239‐residue polyketide synthase nonribosomal‐peptide synthetase (PKS‐NRPS) from <jats:italic>Beauveria bassiana</jats:italic>, was expressed in <jats:italic>Aspergillus oryzae</jats:italic> M‐2‐3. This led to the production of three new compounds, identified as acyl tetramic acids, and numerous minor metabolites. Consideration of the structures of these compounds indicates that the putative C‐terminal thiolester reductase (R) domain does not act as a reductase, but appears to act as a Dieckmann cyclase (DKC). Expression of <jats:italic>tenS</jats:italic> in the absence of a trans‐acting ER component encoded by <jats:italic>orf3</jats:italic> led to errors in assembly of the polyketide component, giving clues to the mode of programming of highly reducing fungal PKS. Coexpression of <jats:italic>tenS</jats:italic> with <jats:italic>orf3</jats:italic> from the linked gene cluster led to the production of a correctly elaborated polyketide. The NRPS adenylation domain possibly shows the first identified fungal signature sequences for tyrosine selectivity.

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