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Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design
Xiaofeng Cai1, Sarah Nowak1, Frank Wesche1
1Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, Frankfurt am Main, 60438, Germany.
Nature Chemistry
|March 25, 2017
Summary
Bacteria produce diverse natural products through unique biosynthesis mechanisms. This study reveals how Photorhabdus and Xenorhabdus bacteria generate chemically diverse rhabdopeptide/xenortide peptides (RXPs) using flexible enzymes.
Area of Science:
- Microbiology
- Biochemistry
- Natural Product Chemistry
Background:
- Organisms like bacteria, fungi, and plants produce diverse natural product libraries.
- Mechanisms underlying the generation of these chemically diverse libraries remain largely unknown.
- Rhabdopeptide/xenortide peptides (RXPs) are exclusively found in entomopathogenic bacteria of the genera Photorhabdus and Xenorhabdus.
Purpose of the Study:
- To elucidate the biosynthetic mechanisms responsible for the chemical diversity of rhabdopeptide/xenortide peptides (RXPs).
- To understand how symbiotic bacteria Photorhabdus and Xenorhabdus generate bioactive RXPs.
Main Methods:
- In vivo and in vitro experiments were conducted.
- Analysis focused on the iterative and flexible use of monomodular nonribosomal peptide synthetases.
- Investigated factors such as substrate promiscuity, enzyme cross-talk, and enzyme stoichiometry.
Main Results:
- Demonstrated that chemical diversity in RXPs arises from the flexible application of nonribosomal peptide synthetases.
- Identified substrate promiscuity, enzyme cross-talk, and enzyme stoichiometry as key contributors to RXP diversity.
- Confirmed these mechanisms through both in vivo and in vitro experimental approaches.
Conclusions:
- Highlighted novel natural mechanisms for the diversification and evolution of natural products.
- Provided significant insights into the biosynthesis of bioactive RXPs in Photorhabdus and Xenorhabdus bacteria.
- Emphasized the role of flexible enzyme usage in generating chemical diversity in microbial natural products.
