Structural basis for the selectivity of the external thioesterase of the surfactin synthetase

Alexander Koglin, Frank Löhr, Frank Bernhard, Vladimir V. Rogov, Dominique P. Frueh, Eric R. Strieter, Mohammad R. Mofid, Peter Güntert, Gerhard Wagner, Christopher T. Walsh, Mohamed A. Marahiel, Volker Dötsch

Research output: Contribution to journalArticlepeer-review

Abstract

Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4′-phosphopantetheine (4′-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4′-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4′-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4′-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain.

Original languageEnglish (US)
Pages (from-to)907-911
Number of pages5
JournalNature
Volume454
Issue number7206
DOIs
StatePublished - Aug 14 2008
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Structural basis for the selectivity of the external thioesterase of the surfactin synthetase'. Together they form a unique fingerprint.

Cite this