Ewa Huszcza

Steroids' transformations in Penicillium notatum culture.

The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15alpha-hydroxylation of 17alpha-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield.

Transformations of testosterone and related steroids by Botrytis cinerea.

Botrytis cinerea (strain AM235) was used to investigate the transformations of testosterone and related steroids. It was found that the position and stereochemistry of the introduced hydroxyl group, as well as the yield of products, depended on the structure of the substrate. Botrytis cinerea converts the examined substrates mainly to 7 alpha-hydroxy derivatives. 1-Dehydrotestosterone was also significantly hydroxylated at a 14 alpha-position.

Biotransformations of Prenylated Hop Flavonoids for Drug Discovery and Production

In this review we aim to present current knowledge on biotransformation of flavonoids from hop cones with respect to type of product, catalyst and conversion. Subsequently, a comparative analysis of biological activity of prenylated hop flavonoids and their biotransformation products has been performed in order to indicate these research efforts that have good potential for application in pharmaceutical industry. There is increasing evidence that the products of biotransformation of hop prenylflavonoids, which have been little studied until recently, can be used as drugs or drug ingredients and also as standards of human drug metabolites. They can also serve as an inspiration for the design and chemical synthesis of new derivatives with higher or different biological activity. Nevertheless, much additional work, among others on determining the mechanism of action in in vivo systems, is needed to open up the way to biomedical application of these compounds.

Surfactin Isoforms from Bacillus coagulans

Abstract Bacillus coagulans has been found to produce several surfactins that are powerful lipopeptide surfactants. Four main components with molecular weights 1007, 1021 and 1035 Da were separated. Their structures have been confirmed by spectrometric and spectroscopic studies and by acid hydrolysis. The compounds were found to represent two pairs of surfactin isoforms in which β-hydroxy-iso-C14 or anteiso-C15 fatty acids are linked to the [Leu7] or [Val7] heptapeptide moiety by both an amide group and a lactone bond.

Transformations of steroids by Beauveria bassiana.

The course of transformations of testosterone and its derivatives, including compounds with an additional C1,C2 double bond and/or a 17α-methyl group, a 17β-acetyl group or without a 19-methyl group, by a Beauveria bassiana culture was investigated. The fungi promoted hydroxylation of these compounds at position 11α, oxidation of the 17β-hydroxyl group, reduction of the C1,C2 or C4,C5 double bonds and degradation of the progesterone side-chain, leading to testosterone. The structure of 4-ene-3-oxo-steroids had no influence on regio- and stereochemistry of hydroxylation. In a similar manner, dehydroepiandrosterone was hydroxylated by Beauveria bassiana at position 11α, however, a small amount of 7α- hydroxylation product was also formed.

Microbial Glycosylation of Daidzein, Genistein and Biochanin A: Two New Glucosides of Biochanin A

Biotransformation of daidzein, genistein and biochanin A by three selected filamentous fungi was investigated. As a result of biotransformations, six glycosylation products were obtained. Fungus Beauveria bassiana converted all tested isoflavones to 4″-O-methyl-7-O-glucosyl derivatives, whereas Absidia coerulea and Absidia glauca were able to transform genistein and biochanin A to genistin and sissotrin, respectively. In the culture of Absidia coerulea, in addition to the sissotrin, the product of glucosylation at position 5 was formed. Two of the obtained compounds have not been published so far: 4″-O-methyl-7-O-glucosyl biochanin A and 5-O-glucosyl biochanin A (isosissotrin). Biotransformation products were obtained with 22%–40% isolated yield.

Microbial Sulfation of 8-Prenylnaringenin

Out of 24 fungal strains tested for their ability to transform 8-prenylnaringenin, Syncephalastrum racemosum was found to convert this phytoestrogen to a sulfate derivative. The conjugation with sulfuric acid observed in this study is paralleled in mammals indicating that microbes can be used to mimic mammalian metabolism.

Biotransformation of the phytoestrogen 8-prenylnaringenin.

In order to select microorganisms capable of transforming the potent phytoestrogen 8-prenylnaringenin, preliminary screening tests on 30 fungal cultures were performed. No reports concerning successful biotransformation of 8-prenylnaringenin by this class of organisms have been known so far. Fusarium equiseti converted 8-prenylnaringenin into 2”-(2”’-hydroxyisopropyl)-dihydrofuran-[2”,3”:7,8]-5,4’-dihydroxyfl avanon in high yield.

The Influence of Glycosylation of Natural and Synthetic Prenylated Flavonoids on Binding to Human Serum Albumin and Inhibition of Cyclooxygenases COX-1 and COX-2

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol (2) and (Z)-6,4’-dihydroxy-4-methoxy-7-prenylaurone (3)) was performed in one step reactions from xanthohumol (1)—major prenylated chalcone naturally occurring in hops. Obtained flavonoids (2–3) and xanthohumol (1) were used as substrates for regioselective fungal glycosylation catalyzed by two Absidia species and Beauveria bassiana. As a result six glycosides (4–9) were formed, of which four glycosides (6–9) have not been published so far. The influence of flavonoid skeleton and the presence of glucopyranose and 4-O-methylglucopyranose moiety in flavonoid molecule on binding to main protein in plasma, human serum albumin (HSA), and inhibition of cyclooxygenases COX-1 and COX-2 were investigated. Results showed that chalcone (1) had the highest binding affinity to HSA (8.624 × 104 M−1) of all tested compounds. It has also exhibited the highest inhibition of cyclooxygenases activity, and it was a two-fold stronger inhibitor than α,β-dihydrochalcone (2) and aurone (3). The presence of sugar moiety in flavonoid molecule caused the loss of HSA binding activity as well as the decrease in inhibition of cyclooxygenases activity.

Microbial Glycosylation of Flavonoids

Flavonoids constitute a large group of polyphenolic compounds naturally found in plants, which have a wide range of biological activity. Although flavonoids are beneficial to human health, their application is limited by their low bioavailability and poor water-solubility. Therefore, recently there has been a particular interest in glycosylated forms of flavonoids, which usually are better soluble, more stable, and more functional compared to their aglycones. Microbial transformation of natural flavonoids may be an attractive way of receiving their glycosylated derivatives in amounts sufficient for the research on the effect of glycoside group on compound properties and for further application of these compounds as ingredients of dietary supplements and pharmaceuticals.