Biotransformation of artemisinin by Aspergillus niger

Abstract

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 3β-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.

Microbial transformation of artemisinin by Aspergillus terreus

“…1). The comparison of the 1 H and 13 C NMR data of product 3 with those of 4α-hydroxy-1-deoxyartemisinin (Parshikov et al 2004; Zhan et al 2015) was in complete agreement. Therefore, product 3 was confirmed to be 4α-hydroxy-1-deoxyartemisinin (Fig.…”

“…Therefore, microbial transformation is a promising route to obtain artemisinin derivatives. There are many reports on microbial transformation of artemisinin by various microorganisms, such as Aspergillus niger , Rhizopus stolonifer , Cunninghamella elegans , Eurotium amstelodami , Mucor polymorphosporus , Penicillium simplicissimum , Streptomyces griseus (Zhan et al 2015; Gaur et al 2014; Goswami et al 2010; Liu et al 2006; Parshikov et al 2004, 2006; Zhan et al 2002). Here, we first report the microbial transformation of artemisinin by A. terreus .…”

Aspergillus niger: A Hundred Years of Contribution to the Natural Products Chemistry

“…In general, the Csp 3 oxidation 24,135-147 is the most widespread reaction that occurs in various structural types of terpenoids, including monoterpenes, diterpenes and sesquiterpenes. Some examples of Csp 2 oxidation, 24,142,[147][148][149][150] C=C dihydroxylation, 24 C=C reduction, 24,150 C=C migration, 24,145,150 C=O reduction, 24,150 hydrolyses, 24 epoxide opening, 24,135,150 ring opening, 24,139,149 elimination, 24,135,148,150 OH oxidation, 24,135,150 acetylation, 24 heterocyclization, 24 dehydrogenation, 24 esterification, 24,142,145 oxidative ring opening, 24 Baeyer-Villiger, 146,148 demethylation, 136 Michael addition, 24 peroxide deoxygenation, 24 O-alkylation, 24 aromatization, 24,139 Beckmann rearrangement, 146 Csp 3 halogenation, 145 CO 2 H reduction (conversion of lactam to CN),…”

“…Artemisinin (237) was also biotransformed by VKM F-1119 strain to produce the new products 3β-hydroxy-4,12-epoxy-1-deoxyartemisinin (238), 3,13-epoxyartemisinin (239) and 4α-hydroxy-1-deoxyartemisinin (240), which display epoxy structures, besides the ring rearranged product artemisinin G (241) (Figure 23). 149 Despite the existence of some studies of microbial transformation of artemisinin and derivatives, it was the first report of epoxidation and rearrangement of artemisinin using microbial strains.…”

Features of Antitumor and Antimalarial Artemisinins Biotransformations

“…Aspergillus niger VKM F-1119 long time was keeped in Olemiss (USA) laboratory(dried slants in work table from2006 to 2015) and as result was infected(Zhan et al, 2015).…”