A fractional factorial design approach has been used to enhance secondary metabolite production by two Penicillium strains. The method was initially used to improve the production of bioactive extracts as a whole and subsequently to optimize the production of particular bioactive metabolites. Enhancements of over 500% in secondary metabolite production were observed for both P. oxalicum and P. citrinum. Two new alkaloids, citrinalins A (5) and B (6), were isolated and identified from P. citrinum cultures optimized for production of minor metabolites.

Recebido em 9/5/07; aceito em 30/11/07; publicado na web em 21/7/08Extracts obtained from 57 marine-derived fungal strains were analyzed by HPLC-PDA, TLC and 1 H NMR. The analyses showed that the growth conditions affected the chemical profile of crude extracts. Furthermore, the majority of fungal strains which produced either bioactive of chemically distinctive crude extracts have been isolated from sediments or marine algae. The chemical investigation of the antimycobacterial and cytotoxic crude extract obtained from two strains of the fungus Beauveria felina have yielded cyclodepsipeptides related to destruxins. The present approach constitutes a valuable tool for the selection of fungal strains that produce chemically interesting or biologically active secondary metabolites.

Chemical investigation of the cytotoxic and anti-tuberculosis active butanone extract obtained from the growth media of the marine-derived fungus Beauveria felina led to the isolation of two new destruxins, [b -MePro] destruxin E chlorohydrin (1) and pseudodestruxin C (3), along with five known cyclic depsipeptides. The structures of the new destruxin derivatives were established by analysis of spectroscopic data, while the absolute configuration of the common amino acid residues was established by Marfey's analysis. The absolute configuration of the 2(R),4(S)-5-chloro-2,4-dihydroxypentanoic acid residue in 1 could be established by application of a J-based configuration method followed by derivatization with R-MPA-Cl and NMR analysis.

New Destruxins from the Marine-Derived Fungus Beauveria felina -[isolation and structure determination]. -(LIRA, S. P.; VITA-MARQUES, A. M.; SELEGHIM, M. H. R.; BUGNI, T. S.; LABARBERA, D. V.; SETTE, L. D.; SPONCHIADO, S. R. P.; IRELAND, C. M.; BERLINCK*, R. G. S.; J. Antibiot. 59 (2006) 9, 553-563; Inst. Quim. Sao Carlos, Univ. Sao Paulo, 13560 Sao Carlos, Sao Paulo, Brazil; Eng.) -H. Toeppel 12-195