Microbial transformation of artemisinin by Aspergillus terreus.

BACKGROUND: Artemisinin (1) and its derivatives are now being widely used as antimalarial drugs, and they also exhibited good antitumor activities. So there has been much interest in the structural modification of artemisinin and its derivatives because of their effective bioactivities. The microbial transformation is a promising route to obtain artemisinin derivatives. The present study focuses on the microbial transformation of artemisinin by Aspergillus terreus. RESULTS: During 6 days at 28 °C and 180 rpm, Aspergillus terreus transformed artemisinin to two products. They were identified as 1-deoxyartemisinin (2) and 4α-hydroxy-1-deoxyartemisinin (3) on the basis of their spectroscopic data. CONCLUSIONS: The microbial transformation of artemisinin by Aspergillus terreus was investigated, and two products (1-deoxyartemisinin and 4α-hydroxy-1-deoxyartemisinin) were obtained. This study is the first to report on the microbial transformation of artemisinin by Aspergillus terreus.

A novel dihydroxylated derivative of artemisinin from microbial transformation.

Microbial transformation of artemisinin (1) by Cunninghamella elegans was investigated. Four isolated products were identified as 6ß-hydroxyartemisinin (2), 7α-hydroxyartemisinin (3), 7ß-hydroxyartemisinin (4), and 6ß,7α-dihydroxyartemisinin (5). The structures were elucidated by spectroscopic and X-ray crystallographic analysis. Product 5 is a novel compound and being reported here for the first time. It features two hydroxyl groups in its structure, and this is the first report on dihydroxylation of the artemisinin skeleton. Quantitative structure-activity relationship and molecular modeling studies indicate the modification of artemisinin skeleton will increase antimalarial activity and water solubility. The chemical syntheses of artemisinin derivatives at C6 or C7 position are impossible due to the lack of functional groups. 6ß,7α-Dihydroxyartemisinin is hydroxylated at both 6ß- and 7α-positions of artemisinin skeleton at the same time. Therefore, this new compound would be a good scaffold for further structural modification in the search for more potent antimalarial drugs.

Efficient production of nonactin by Streptomyces griseus subsp. griseus.

Here we report the production of the cyclic macrotetrolide nonactin from the fermentation culture of Streptomyces griseus subsp. griseus. Nonactin is a member of a family of naturally occurring cyclic ionophores known as the macrotetrolide antibiotics. Our fermentation procedure of Streptomyces griseus was performed at 30 °C and 200 rev·min(-1) for 5 days on a rotary shaker. Diaion HP-20 and Amberlite XAD-16 were added to the fermentation medium. Isolated yield of nonactin was up to 80 mg·L(-1) using our methodology. Nonactin is commonly known as an ammonium ionophore and also exhibits antibacterial, antiviral, and antitumor activities. It is also widely used for the preparation of ion-selective electrodes and sensors. Chemical synthesis of nonactin has been achieved by some groups; however, overall yields are very low, making efficient biosynthesis an attractive means of production.

Biotransformation of artemisinin by Aspergillus niger.

Biotransformation of artemisinin (1) by Aspergillus niger was investigated. During 12 days at 28 °C and pH 6.0, A. niger transformed artemisinin into four products. They were identified as 3ß-hydroxy-4,12-epoxy-1-deoxyartemisinin (2), artemisinin G (3), 3,13-epoxyartemisinin (4), and 4α-hydroxy-1-deoxyartemisinin (5). Products 2 and 4 are new compounds and are being reported here for the first time. The product 4 contains a 3,13-epoxy structure. This is the first report of epoxidation of artemisinin using microbial strains. The product 4 still has an intact peroxide bridge and therefore can be used as a scaffold for further structural modification using chemical and biological methods in the search for new antimalarial drugs.

Pseudomerohedrally twinned monoclinic structure of unfolded 'free' nonactin: comparative analysis of its large conformational change upon encapsulation of alkali metal ions.

The title compound, C40H64O12, crystallizes in a pseudomerohedrally twinned primitive monoclinic cell with similar contributions of the two twin components. There are two symmetry-independent half-molecules of nonactin in the asymmetric unit. Each molecule has a pseudo-S4 symmetry and resides on a crystallographic twofold axis; the axes pass through the molecular center of mass and are perpendicular to the plane of the macrocycle. The literature description of the room-temperature structure of nonactin as an order-disorder structure in an orthorhombic unit cell is corrected. We report a low-temperature high-precision ordered structure of ;free' nonactin that allowed for the first time precise determination of its bond distances and angles. It possesses an unfolded and more planar geometry than its complexes with encapsulated Na+, K+, Cs+, Ca2+ or NH4+ cations that exhibit more isometric overall conformations.