Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design.
The production of natural product compound libraries has been observed in nature for different organisms such as bacteria, fungi and plants; however, little is known about the mechanisms generating such chemically diverse libraries. Here we report mechanisms leading to the biosynthesis of the chemically diverse rhabdopeptide/xenortide peptides (RXPs). They are exclusively present in entomopathogenic bacteria of the genera Photorhabdus and Xenorhabdus that live in symbiosis with nematodes delivering them to insect prey, which is killed and utilized for nutrition by both nematodes and bacteria. Chemical diversity of the biologically active RXPs results from a combination of iterative and flexible use of monomodular nonribosomal peptide synthetases including substrate promiscuity, enzyme cross-talk and enzyme stoichiometry as shown by in vivo and in vitro experiments. Together, this highlights several of nature's methods for diversification, or evolution, of natural products and sheds light on the biosynthesis of the bioactive RXPs.
Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, Frankfurt am Main, 60438, Germany.
Xiaofeng
X
Cai
Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, Frankfurt am Main, 60438, Germany.
Sarah
S
Nowak
Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, Frankfurt am Main, 60438, Germany.
Frank
F
Wesche
Institute of Pharmaceutical Biology, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Iris
I
Bischoff
Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Socinstrasse 57, 4051 Basel, Switzerland.|University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
Marcel
M
Kaiser
Institute of Pharmaceutical Biology, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Robert
R
Fürst
Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, Frankfurt am Main, 60438, Germany.|Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt, Max-von-Laue-Strasse 15, Frankfurt am Main, 60438, Germany.
Helge B
0000-0001-6048-5909
HB
Bode
D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D020637:Photorhabdus / Q000378:metabolism*; D020593:Xenorhabdus / Q000378:metabolism*
D001688:Biological Products; D019151:Peptide Library; D010455:Peptides