Biotransformation of steroids by entomopathogenic strains of Isaria farinosa

Abstract

BackgroundSteroid compounds are very interesting substrates for biotransformation due to their high biological activity and a high number of inactivated carbons which make chemical modification difficult. Microbial transformation can involve reactions which are complicated and uneconomical in chemical synthesis, and searching for a new effective biocatalyst is necessary. The best known entomopathogenic species used in steroid modification is Beauveria bassiana. In this study we tested the ability of Isaria farinosa, another entomopathogenic species, to transform several steroids.ResultsTwelve strains of the entomopathogenic filamentous fungus Isaria farinosa, collected in abandoned mines located in the area of the Lower Silesian Voivodeship, Poland, from insects’ bodies covered by fungus, were used as a biocatalyst. All the tested strains effectively transformed dehydroepiandrosterone (DHEA). We observed 7α- and 7β-hydroxy derivatives as well as changes in the percentage composition of the emerging products. Due to the similar metabolism of DHEA in all tested strains, one of them was selected for further investigation. In the culture of the selected strain, Isaria farinosa KCh KW1.1, transformations of androstenediol, androstenedione, adrenosterone, 17α-methyltestosterone, 17β-hydroxyandrost-1,4,6-triene-3-one and progesterone were performed. All the substrates were hydroxylated with high yield and stereoselectivity. We obtained 6β-hydroxyandrost-4-ene-3,11,17-trione, 15α,17β-dihydroxy-6β,7β-epoxyandrost-1,4-diene-3-one and 6β,11α-dihydroxyprogesterone. There is no evidence of either earlier microbial transformation of 17β-hydroxyandrost-1,4,6-triene-3-one or new epoxy derivatives.ConclusionsIsaria farinosa has a broad spectrum of highly effective steroid hydroxylases. The obtained 7-hydroxydehydroepiandrosterone has proven high biological activity and can be used in Alzheimer’s disease and as a key intermediate in the synthesis of aldosterone antagonists. Transformation of progesterone leads to high yield of 6β,11α-dihydroxyprogesterone and it is worth further study.

Culture conditions and nutrition requirements for the mycelial growth of Isaria farinosa (Hypocreales: Cordycipitaceae) and the altitude effect on its growth and metabolome

“…farinosa 2 , the study of I . farinosa intensified, including not only its virulence characteristics 3 , 4 , fungicide 5 , 6 , biochemical characterisation 7 , biotransformation activity 8 and molecular biology 9 , 10 but also its secondary metabolites and pharmacological activity 11 .…”

Glycosylation of 3-Hydroxyflavone, 3-Methoxyflavone, Quercetin and Baicalein in Fungal Cultures of the Genus Isaria

“…To obtain flavonoid glycosides we used four flavonoid substrates and three strains of entomopathogenic filamentous fungi, which were isolated from the environment. Detailed characteristics of the strains that we used can be found in our previous publications [ 44 , 45 ].…”

“…Full characteristics of fungal strains I. fumosorosea KCH J2 and I. farinosa J1.4 and J1.6 are included in our previous publications [ 44 , 45 ]. The microorganisms were maintained on potato slants at 4 °C and freshly subcultured before use in the experiments.…”

Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

“…Hydroxylation at C-7 produces very useful hydroxysteroids of pharmacological value (32,33). Although many fungi have been reported to mediate 7-hydroxylation of steroids (34)(35)(36)(37)(38)(39)(40)(41)(42), low stereoselectivity (7␣/7␤) (38,41) and side hydroxylation reactions (37,42) have often been observed, thus presenting great challenges in developing highly regio-and stereoselective 7-hydroxylation processes of steroidal compounds. CYP5150AP3 favors the 7␤-hydroxylation of 11-deoxycortisol, a 3-keto-4-en-C 21 steroid, and may serve as a starting point for addressing these challenges.…”