Koningiopisins A–H, Polyketides with Synergistic Antifungal Activities from the Endophytic Fungus Trichoderma koningiopsis

Abstract

Eight new fungal polyketides named koningiopisins A–H (1–8) and four previously known polyketides (9–12) were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH 30 002. Their structures were elucidated using extensive spectral data interpretation, and their antifungal and synergistic activities were also evaluated. Koningiopisin C (3) exhibited in vitro antifungal activity against the phytopathogenic fungus Plectosphaerella cucumerina with an MIC of 16 µg/mL. Although the antifungal activities of single compounds were not obvious, a mixture of six compounds (4–9) exhibited potent synergistic antifungal activity against P. cucumerina with an MIC of 16 µg/mL, and the antifungal activity of the mixture of any two compounds with a 1 : 1 ratio was better than that observed from the individual compound. The synergistic biological activity of the metabolites in YIM PH 30 002 demonstrates the significant ecological function of the endophyte for its host plant, and provides additional insight into the search for and development of agents for biological control.

Key words

Trichoderma koningiopsis - Hypocreaceae - polyketide - antifungal activity - synergistic activity

^* These two authors contributed equally to this paper.

• References

• 1 Druzhinina IS, Seidl-Seiboth V, Herrera-Estrella A, Horwitz BA, Kenerley CM, Monte E, Mukherjee PK, Zeilinger S, Grigoriev IV, Kubicek CP. Trichoderma: the genomics of opportunistic success. Nat Rev Microbiol 2011; 9: 749-759
• 2 Samuels GJ. Trichoderma: a review of biology and systematics of the genus. Mycol Res 1996; 100: 923-935
• 3 Mukherjee PK, Horwitz BA, Kenerley CM. Secondary metabolism in Trichoderma – a genomic perspective. Microbiology 2012; 158: 35-45
• 4 Reino JL, Guerrero RF, Hernandez-Galan R, Collado IG. Secondary metabolites from species of the biocontrol agent Trichoderma . Phytochem Rev 2008; 7: 89-123
• 5 Ding G, Wang HL, Li L, Chen AJ, Chen L, Chen H, Zhang HW, Liu XZ, Zou ZM. Trichoderones A and B: two pentacyclic cytochalasans from the plant endophytic fungus Trichoderma gamsii . Eur J Org Chem 2012; 13: 2516-2519
• 6 Sun Y, Tian L, Huang J, Ma HY, Zheng Z, Lv AL, Yasukawa K, Pei YH. Trichodermatides A–D, novel polyketides from the marine-derived fungus Trichoderma reesei . Org Lett 2008; 10: 393-396
• 7 Song FH, Dai HQ, Tong YJ, Ren B, Chen CX, Sun N, Liu XY, Bian J, Liu M, Gao H, Liu HW, Chen XP, Zhang LX. Trichodermaketones A–D and 7-O-methylkoninginin D from the marine fungus Trichoderma koningii . J Nat Prod 2010; 73: 806-810
• 8 Vinale F, Girona IA, Nigro M, Mazzei P, Piccolo A, Ruocco M, Woo S, Rosa DR, Herrera CL, Lorito M. Cerinolactone, a hydroxy-lactone derivative from Trichoderma cerinum . J Nat Prod 2012; 75: 103-106
• 9 Keswani C, Mishra S, Sarma BK, Singh SP, Sing HB. Unraveling the efficient applications of secondary metabolites of various Trichoderma spp. Appl Microbiol Biotechnol 2014; 98: 533-544
• 10 Souza ADL, Rodrigues-Filho E, Souza AQ, Pereira JO, Calgarotto AK, Maso V, Marangoni S, Silva SL. Koninginins, phospholipase A₂ inhibitors from endophytic fungus Trichoderma koningii . Toxicon 2008; 51: 240-250
• 11 Liu G, Wang ZQ. Total synthesis of koninginin D, B and E. Synthesis 2001; 1: 119-127
• 12 Almessi F, Ghisalbertmi EL, Narbey MJ. New antibiotics from strains of Trichoderma harzianum . J Nat Prod 1991; 54: 396-402
• 13 Xu XX, Zhu YH. Total synthesis of koninginin A and its diastereoisomer. Tetrahedron Lett 1995; 36: 9173-9176
• 14 Cutler HG, Cutler SJ, Ross SA, Sayed KE, Dugan FM, Bartlett MG, Parker SR. Koninginin G, a new metabolite from Trichoderma aureoviride . J Nat Prod 1999; 62: 137-139
• 15 Zhang GJ, Wu GW, Zhu TJ, Kurtan T, Mandi A, Jiao JY, Li J, Qi X, Gu QQ, Li DH. Meroterpenoids with diverse ring systems from the sponge-associated fungus Alternaria sp. JJY-32. J Nat Prod 2013; 76: 1946-1957