SurE is a trans-acting thioesterase cyclizing two distinct non-ribosomal peptides

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Non-ribosomal peptides (NRPs) are synthesized by large multi-modular enzymes.
• Thioesterases (TEs) are crucial for releasing completed NRPs from assembly lines.
• Surugamide biosynthesis involves a unique offloading mechanism.

Purpose of the Study:

• To characterize the novel thioesterase SurE involved in surugamide biosynthesis.
• To investigate the substrate specificity and cyclization activity of SurE.
• To understand the role of SurE in the broader context of NRP assembly line offloading.

Main Methods:

• Biochemical assays to determine enzyme activity.
• Analysis of substrate specificity using various NRP precursors.
• Homology modeling and structural analysis to understand enzyme-substrate interactions.

Main Results:

• SurE functions as a stand-alone thioesterase, distinct from typical TE domains within NRP synthetases.
• SurE exhibits broad substrate tolerance, efficiently cyclizing structurally unrelated substrates.
• The enzyme's homology to penicillin-binding proteins (PBPs) suggests potential mechanistic links.

Conclusions:

• SurE is a versatile offloading enzyme with significant substrate flexibility.
• The discovery of SurE expands our understanding of NRP biosynthesis and enzyme evolution.
• SurE's unique properties offer potential for biotechnological applications in peptide synthesis.