Enhancement of antibiotic and secondary metabolite detection from filamentous fungi by growth on nutritional arrays

被引:91
作者
Bills, G. F. [1 ]
Platas, G. [1 ]
Fillola, A. [1 ]
Jimenez, M. R. [1 ]
Collado, J. [1 ]
Vicente, F. [1 ]
Martin, J. [1 ]
Gonzalez, A. [1 ]
Bur-Zimmermann, J. [2 ]
Tormo, J. R. [1 ]
Pelaez, F. [1 ]
机构
[1] Merck Sharp & Dohme Espana SA, Ctr Invest Basica, E-28027 Madrid, Spain
[2] Zimmermann Equipos Invest SL, Navalafuente, Spain
关键词
antifungals; high throughput screening; microfermentation; OSMAC; secondary metabolite induction;
D O I
10.1111/j.1365-2672.2008.03735.x
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aims: We asked to what extent does the application of the OSMAC (one strain, many compounds) approach lead to enhanced detection of antibiotics and secondary metabolites in fungi? Protocols for bacterial microfermentations were adapted to grow fungi in nutritional arrays. Methods and Results: Protocols for microfermentations of non-sporulating fungi were validated using known antifungal-producing fungi. Detection of antifungal activity was often medium dependent. The effects of medium arrays and numbers of strains on detection of antifungal signals were modelled by interpolation of rarefaction curves derived from matrices of positive and negative extracts. Increasing the number of fermentation media for any given strain increased the probability of detection of growth inhibition of Candida albicans. Increasing biodiversity increased detection of antifungal phenotypes, however, nutritional arrays could partly compensate for lost antibiotic phenotypes when biodiversity was limiting. Conclusions: Growth and extraction in microtiter plates can enable a discovery strategy emphasizing low-cost medium arrays that can better exploit the metabolic potential of strains. Significance and Impact of the Study: Increasing fermentation parameters raise the probability of detecting bioactive metabolites from strains. The protocols can be used to pre-select strains and their growth conditions for scale up that will most likely yield antibiotics and secondary metabolites.
引用
收藏
页码:1644 / 1658
页数:15
相关论文
共 43 条
[1]   Influence of water activity and nutrients on growth and production of squalestatin S1 by a Phoma sp. [J].
Aldred, D ;
Magan, N ;
Lane, BS .
JOURNAL OF APPLIED MICROBIOLOGY, 1999, 87 (06) :842-848
[2]   Diversity and host range of foliar fungal endophytes: Are tropical leaves biodiversity hotspots? [J].
Arnold, A. Elizabeth ;
Lutzoni, F. .
ECOLOGY, 2007, 88 (03) :541-549
[3]  
Barrios-Gonzalez J, 1996, Biotechnol Annu Rev, V2, P85, DOI 10.1016/S1387-2656(08)70007-3
[4]   Production of fungal antibiotics using polymeric solid supports in solid-state and liquid fermentation [J].
Bigelis, Ramunas ;
He, Haiyin ;
Yang, Hui Y. ;
Chang, Li-Ping ;
Greenstein, Michael .
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY, 2006, 33 (10) :815-826
[5]   Conspecificity of the cerulenin and helvolic acid producing 'Cephalosporium caerulens', and the hypocrealean fungus Sarocladium oryzae [J].
Bills, GF ;
Platas, G ;
Gams, W .
MYCOLOGICAL RESEARCH, 2004, 108 :1291-1300
[6]  
Bode HB, 2002, CHEMBIOCHEM, V3, P619, DOI 10.1002/1439-7633(20020703)3:7<619::AID-CBIC619>3.0.CO
[7]  
2-9
[8]  
Buckingham J.E., 2007, Dictionary of natural products
[9]   Using jasplakinolide to turn on pathways that enable the isolation of new chaetoglobosins from Phomospis asparagi [J].
Christian, OE ;
Compton, J ;
Christian, KR ;
Mooberry, SL ;
Valeriote, FA ;
Crews, P .
JOURNAL OF NATURAL PRODUCTS, 2005, 68 (11) :1592-1597
[10]   High-throughput culturing of fungi from plant litter by a dilution-to-extinction technique [J].
Collado, Javier ;
Platas, Gonzalo ;
Paulus, Barbara ;
Bills, Gerald F. .
FEMS MICROBIOLOGY ECOLOGY, 2007, 60 (03) :521-533