Find new weapons on the battlefields of nature Genomic research opens up a treasure trove of active small molecules hidden in insect pathogenic bacteria

The interaction of microorganisms with higher eukaryotes plays an important role in driving biogeochemical cycles, maintaining species coexistence and biodiversity, promoting host evolution, and maintaining normal physiological states of hosts. Interactions between these species are regulated by a myriad of unknown small molecules(also known as natural products).

The research team, co-led by Dr. Yiming Shi and Professor Helge Bode of the Max Planck Institute for Terrestrial Microbiology in Germany, conducted a systematic analysis of the “dark matter” of microbial biosynthesis and its biological functions, thus laying a solid foundation for the future discovery and screening of microbial natural products.

On April 25, 2022, the study was published in Nature Chemistry under the title “Global analysis of biosynthetic gene clusters reveals conserved and unique natural products in entomopathogenic nematode-symbiotic bacteria.”

Bacteria mediate their interactions with other biological species by synthesizing and secreting large quantities of natural products. In general, however, it is difficult to trace which bacteria produce what compounds and what functional properties the compounds have. The bacterial-nematode-insect inter-ecosystem centered on symbiotic bacteria Xenorhabdus and Photorhabdus is an ideal model for solving complex chemical ecology problems. This is because symbiotic bacteria live in a different way in the natural environment, where symbiotic bacteria and specific nematode hosts mutually benefit and coexist to infect and kill insect larvae in the soil; secondly, in the laboratory environment, symbiotic bacteria, nematodes and insects can be rapidly cultured and multiplied under conventional conditions; and finally, a variety of efficient genetic manipulation systems have been developed for symbiotic bacterial gene editing.

For the first time, the researchers systematically studied symbiotic bacteria by combining pan-genome and gene cluster similarity cluster network analysis, solving two core questions in the microecological environment: “Which gene clusters in the symbiotic bacterial genome are responsible for synthesizing natural products with important ecological functions” and “which gene clusters are highly conserved in the population and which are unique”.

The research team, co-led by Dr. Yiming Shi and Professor Helge Bode, found that symbiotic bacterial populations encode a thousand clusters of biosynthetic genes, more than half of which are unknown. Through homologous expression and chemical structure analysis, the research team found three highly conserved natural products. However, what benefits do nematode hosts derive from these bacterial products? Dr. Yiming Shi explains: “Our bioactivity assessment shows that the most highly conserved bacterial natural products are eukaryosome inhibitors, which may cause insect cell cycle disruption and cause apoptosis. The other two highly conserved products are toxicity factors against insects and immune system inhibitors in insects. Therefore, highly conserved bacterial natural products involve the early stages of bacterial-nematode symbiotes invading insect larvae, helping nematodes to kill insects quickly, and our findings initially reveal the way species play between species in the microecological environment at the molecular function level. Professor Helge Bode believes that “these new active natural products stand out among countless symbiotic bacterial natural products not only because they have novel chemical structures and modes of action, but also because they are widely present in different bacterial taxa.” This means that there may be universal chemical weapons in the bacterial community (at least gram-negative bacteria). ”

The activity assessment of the paper was carried out in collaboration with the research group of Professor Yonggyun Kim of Andong National University in South Korea, the research group of Professor Michael Groll of the Technical University of Munich in Germany, and the research group of Professor Rolf Müller of the Helmholz Saar Institute of Medicine (HIPS).

In addition to revealing the natural products of important ecological functions, the research work also excavates the huge biosynthetic potential of symbiotic bacteria, providing new clues for the treatment of leading compounds for human diseases. At the same time, the research ideas and methods of this work are extremely ubiquitous, providing an important reference for accelerating the discovery and refinement of natural products in the microbiome of other ecosystems. (Source: Science Network)

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