Termine Fungiculture – A Hidden Treasure Trove
Until 2022
Since the development of microbes and higher eukaryotes coevolution has resulted in specific interaction mechanisms. It is well known that symbiotic bacteria and fungi influence the life cycle, and are essential for the homeostasis of many eukaryotes. However, in most cases, the factors driving and influencing the cross-kingdom interactions are unknown.
We focus on the structural identification of microbial chemical mediators that are important to maintain the symbiotic life style of the producing organisms.
To study the chemical signals we apply state-of-the-art analytical tools:
- Analytical Chemistry (UHPLC, UHPLC-MS, NMR, MALDI etc.)
- Genome Mining and Molecular Biology
- Organic Synthesis (total synthesis and natural product derivatization)
Natural Products of Microbial Symbionts of Termites
Fungus-growing termites rear a symbiotic fungus as a food source in specialized combs. Termites have developed several strategies to combat invading fungi species, which can be life-threatening to the insect colony. Especially defensive symbionts support the homeostasis of the colony by secretion of selective antimicrobial and antifungal products.
Natural Products of Microbial Symbionts of Hydractinia
Natural products present in bacterial biofilm induce morphogenesis of larvae of the marine hydroid polyp Hydractinia echinata.
Head
Christine Beemelmanns
HeadTermites and their symbionts
Studying the microbiome of social insects, such as termites, helps to identify new aspects of small-molecule mediated symbiotic relations. At the same time it serves platform to identify new antibacterial and antifungal agents.
Fungus-growing termites
The fungus-growing termite system is a prime example of multilateral symbiosis. The ancient farming symbiosis involves a termite host (Macrotermitinae), a specialized fungal mutualist (Termitomyces) maintained in an optimized fungal garden system (fungus comb), the presence of complex and highly adapted bacterial communities within the insect gut and fungus comb, and the co-evolved garden weed (Pseudoxylaria).
Natural products from protective symbionts
Within this project, we aim to isolate, characterize and understand the role of natural products produced by microorganisms associated with fungus-growing termites. We used various different culturing techniques to isolate termite-associated microbes and pursued the whole genome sequence of several key isolates. Subsequent chemical analysis of our isolates in axenic and co-cultures revealed several new natural product classes showing a diverse set of biological activities.
Natural products
Biosynthetic pathway analysis
We have sequenced the genomes of selected new microbial species to analyze their biosynthetic potential and potentially detect new natural products. The comparative analysis of the acquired genomic information likely reveals new biosynthetic enzymes and new biochemical transformations.
Documentation
Wie ein Antibiotikacocktail Insekten schützt
Funding
- ChemBioSys (DFG) seit 2016
- BiBiMac (DFG-ANR) ab 2018
Our collaborations
- Group of Assoc. Prof. M. Poulsen (University of Copenhagen, Denmark),
- Group of Assoc. Prof. K.-H. Kim (Sungkyunkwan University, Republic of Korea)
- Bio Plant Facility (HKI)
- Jena Microbial Resource Collection (HKI)
Microbial Symbionts of Hydractinia
Microbes associated with marine invertebrates are well-known to harbor an enormous biosynthetic potential. We combine new bioassays, genome sequencing and mining strategies to identify the encoded secondary metabolites with unique chemical scaffolds and potential pharmaceutical application.
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shell overgrown with H. echiniata -
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Marine bacteria
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wild isolates of marine bacteria -
pure isolates of marine bacteria -
Pseudoalteromonas sp.
Microorganisms protect and shape the colonial hydroid polyp Hydraktinia
Morphogenic Signaling Molecules
More and more examples show that bacterially produced small molecules contribute to the host’s fitness and development by acting as biological information carrier to maintain and modulate the multilateral interaction network. But fully characterized examples are still rare, and the mode-of-actions of those molecules are often not well understood.
Model system Hydractinia echinata
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shell overgrown with H. echiniata -
shell overgrown with H. echiniata -
H. echinata
The life cycle
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fertilized oocytes -
larvae -
primary polyp
We are investigating the model system Hydractinia echinata, a marine hydroid polyp, to identify key metabolites that induce biofouling.
The life cycle of the marine hydroid polyp H. echinata has a motile (larvae) and sessil reproductive phase (polyp). The irreversible morphogenesis from the motile larvae to the sessile primary polyp is induced by specific molecules from Pseudoalteromonas spp. But the structure determination and and mode of action of the signaling molecules has been so far elusive. We use a broad range of molecular biology methods to identify the bacterial cues and the receptor in the marine hydroid polyp to understand the interaction mechanisms in more detail.
Natural product synthesis and derivatisation
Many natural products are only produced in minor amounts and a full structural characterization is nearly impossible. In addition, many pharmaceutically interesting compounds are too toxic and need derivatisation to improve their pharmacological properties.
Therefore, we are establishing synthetic strategies towards sphingoid-type natural products and functionalized lipids, which represent important signaling molecules in our ecological mdoel systems.
Synthesis of new NRPS-derived natural products
Based on a comparative genome analysis, we were able to isolate a new natural product - barnesin A. Further bioactivity studies showed that barnesin A is a cysteine protease inhibitor with nanomolar activity. The total synthesis enabled further structural activity studies.
For more details, see Maja's article in ACS ChemBio!
Publications
(2019)
Stereoselective synthesis of unnatural (2S,3S)-6-hydroxy-4-sphingenine-containing sphingolipids.
Org Biomol Chem 17(29),
6964-6969.
(2019)
Disease-free monoculture farming by fungus-growing termites.
Sci Rep 9(1),
8819.
(2019)
Ursprung und Funktionen der Sphingolipide.
Nachrichten aus der Chemie 67(2),
66-70.
(Review)
(2019)
Spirocyclic cladosporicin A and cladosporiumins I and J from a Hydractinia-associated Cladosporium sphaerospermum SW67.
Org Chem Front 6,
1084-1093.
(2019)
Fridamycin A, a microbial natural product, stimulates glucose uptake without inducing adipogenesis.
Nutrients 11(4),
765.
(2018)
Natural products from Actinobacteria associated with fungus-growing termites.
Antibiotics 7(3),
83.
(2018)
Biocatalytic production of psilocybin and derivatives in tryptophan synthase-enhanced reactions.
Chem Eur J 24(40),
10028-10031.
(2018)
Iterative L-tryptophan methylation in Psilocybe evolved by sub-domain duplication.
ChemBioChem
[Accepted]
(2018)
Expanding the rubterolone family: Intrinsic reactivity and directed diversification of PKS‐derived pyrans.
Chem Eur J 24(44),
11319-11324.
(2018)
Precursor-directed diversification of cyclic tetrapeptidic pseudoxylallemycins.
ChemBioChem 19(21),
2307-2311.