Genome-Guided Metabolomic Profiling of Peptaibol-Producing Trichoderma
Peptaibols are linear fungal peptides featuring α,α-dialkylated amino acids (e.g., α-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus sp. SK1-7, isolated from decaying wood, revealed the production of previously described trichorozin IV (), along with novel SF4-type peptaibol (trichorozin V). The structures of these compounds were elucidated through MS analysis, NMR study and advanced Marfey's method. The genome of sp. SK1-7 harbors two PKS-NRPS hybrid gene clusters containing 14 and 18 adenylation domains. Analysis of the modular architecture suggested that trichorozins are synthesized by a 14-module protein via a module skipping mechanism. Genome mining revealed several types of short peptaibol synthase architectures (10-14 adenylation domains) across various species, accompanied by similar long peptaibol synthases. Furthermore, putative Aib/Iva biosynthesis machinery in was identified, showing specific architectures potentially involved in regulating peptaibol biosynthesis. Feeding experiments demonstrated that peptaibol production depends on the ratio of Iva/Aib. The isolated compounds exhibited moderate antibacterial and cytotoxic activities along with a synergistic effect when combined with membrane-targeting antibiotics. Our findings suggest that genome-guided approaches hold promise for further development of peptabiotics with a wide range of applications, including antibiotic adjuvants.
Sinichich AA, Krivonos DV, Baranova AA, Zhitlov MY, Belozerova OA, Lushpa VA, Vvedensky AV, Serebryakova MV, Kalganova AI, Kudzhaev AM, Prokopenko YA, Sinelnikova SS, Trusova EA, Kovalchuk SI, Ilina EN, Terekhov SS, Alferova VA
Department of Peptide and Protein Technologies, Laboratory of antibiotic resistance, Department of structural biology, Laboratory of biomolecular NMR-spectroscopy, Department of Genomics and Postgenomic Technologies, Laboratory of molecular bases of embryogenesis, Department of molecular bases of neurosignalization, Department of Biomolecular Chemistry, Laboratory of Rational Design of Chemotherapeutic Agents, Department of functioning of living systems, Laboratory of molecular design and synthesis, Laboratory of bioinformatics approaches in combinatorial chemistry and biology
Нет данных о цитировании
Данные статьи проверены модераторами 2025-06-27
Список научных проектов, где отмечена публикация
- Oncotheranostics and problems of resistance to antitumor and antibacterial drugs (April 23, 2024 — December 31, 2026). Deyev S.M., Alekseeva N.A., Alekseeva L.G., Aliper E.T., Alferova V.A., Andrianova A.G., Babkova Y.S., Baranova A.A., Baranova M.N., Belogurov A.A., Bogachuk A.P., Bocharov E.V., Burenina O.Y., Bychkov M.L., Veretenenko I.I., Volkov D.V., Gabibov A.G., Gordeeva V.D., Gorelik L.V., Gryaznova O.Y., Gulyak E.L., Deryabin A.S., Dobrochaeva K.L., Evpak A.S., Egorova N.S., Emel'yanov E.A., Ermolaeva E.O., Efremov R.G., Zhitlov M.Y., Zhuchkov V.A., Zakharova M.Y., Zvyagin A.V., Zelepukin I.V., Zinchenko A.A., Kalganova A.I., Kirichenko A.V., Kirpichnikov M.P., Knorre V.D., Kovaleva D.K., Kovalenko E.I., Kokaeva I.S., Konovalova E.V., Konshina A.G., Korotkova N.A., Korshun V.A., Kotel'nikova O.V., Kotelnikova P.A., Kravchenko T.V., Krylov N.A., Kudriaeva A.A., Kuzmina O., Kurbatskaya I.N., Lazarev I.V., Logvinov A.S., Lyukmanova E.N., Mazur R.V., Mallaev R.A., Mirzoeva N.Z., Mirkasymov A.B., Musatova O.E., Nechaeva A.M., Nikitin T.D., Nikonova A.V., Nolde D.E., Odzhomoko L.O., Orlova D.A., Panina I.S., Pakhomov A.A., Pahomova T.E., Pizhonkov N.A., Pipiya S.O., Polyansky A.A., Pohorukov D.A., Prokopenko Y.A., Proshkina G.M., Rodionov V.I., Rotanova T.V., Rubcov Y.P., Ryabukha Y.A., Savateeva N.S., Sapozhnikova K.A., Serova E.V., Sinichich A.A., Smirnov I.V., Sogomonyan A.S., Spallone A., Stepanova (Ukrainskaya) V.M., Streltsova M.A., Sutugin Y.A., Terekhov S.S., Frolova A.Y., Khavroshechkina E.V., Khodarovich Y.M., Kholodenko R.V., Tsetlin V.I., Chumakov S.P., Shilova P.A., Shlepova O.V., Shramova E.I., Shul'ga A.A.. Grant, Budget.
: 
: 40565070