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Fungal transformation of a norethisterone (17a-ethynylestra-4-en-17ß-ol-3-one) (1) by using Macrophomina phaseolina and Paecilomyces variotii was studied. A new metabolite, 17a-hydroxymethyl-androst-4-en-11ß-ol-3-one-17ß-acetate (2) with novel changes and a known metabolite, 17a-ethynylestradiol (3) were obtained from 1 by using M. phaseolina and P. variotii, respectively. Based on various spectroscopic techniques, the structures of both metabolites were characterized. The antimicrobial activities of 1-3 were also evaluated. Compound 1 was found to be moderately active against Salmonella paratyphi while 1-3 were almost inactive against other microorganisms. [ABSTRACT FROM AUTHOR]

• Fungal transformation of kaempulchraol E (1) was performed by Rhizopus oryzae KX685359. • Two new diterpenoids 2 and 3 along with roscorane B (4) were produced. • Compound 2 was confirmed via X-ray diffraction analysis. • Compound 4 showed potent toxicity against HSC-2 cell lines. Fungal transformation of the diterpenoid kaempulchraol E (1) by Rhizopus oryzae KX685359 afforded two trihydroxlated isopimaradienes: 2α,6β,14β-trihydroxy-isopimara-8(9),15-diene (2) and 2α,6β,14α-trihydroxy-isopimara-8(9),15-diene (3) in addition to the known metabolite roscorane B (4). Chemical structures were established by spectroscopic techniques including: HRMS, FT-IR and 1D- & 2D-NMR. The structure of 2 was confirmed by single-crystal, X-ray diffraction analysis. Bio-transformed metabolites as well as the substrate originally isolated from Kaempheria galanga were tested against two cancer cell lines: HSC-2 and B16-BL6. Compounds 4 showed greater toxicity than the original plant derived diterpene (IC 50 54.08 ± 0.05 versus 96.05 ± 0.03 μM, respectively) when assayed against the HSC-2 cell line. This study confirms the role of fungal transformations in developing novel natural products with efficacious biological activities. [ABSTRACT FROM AUTHOR]

Abstract: Advances in protoplast technology underpinned many crucial developments in our understanding of the molecular biology of filamentous fungi. This review follows one of these developments, namely the discovery and analysis of difuran toxin gene clusters. Our understanding of the biosynthetic pathway of the agriculturally important toxin, aflatoxin, has been dramatically enhanced by the use of protoplasts and protoplast-based gene transformation methods. Since the identification of the first pathway genes by complementation of mutants with transforming DNA, transformation has continued to play a critical role in the elucidation of gene function and regulation. But despite the wealth of knowledge accumulated so far some fundamental questions remain to be answered. How did these gene clusters evolve? What is the biological role of aflatoxin? The discovery of homologues of aflatoxin genes in other fungal species such as the pine needle pathogen Dothistroma septosporum may help to shed some light on these questions. [Copyright &y& Elsevier]