BIOTECHNOLOGICAL PRODUCTS AND PROCESS ENGINEERING Biotransformation of artemisinin by Aspergillus niger Yulian Zhan & Hua Liu & Yunshan Wu & Pingying Wei & Zhencheng Chen & John S. Williamson Received: 18 January 2015 /Revised: 3 February 2015 /Accepted: 6 February 2015 /Published online: 25 February 2015 # Springer-Verlag Berlin Heidelberg 2015 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 3 β -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 re- ported 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 scaf- fold for further structural modification using chemical and biological methods in the search for new antimalarial drugs. Keywords Biotransformation . Artemisinin . Antimalarial drugs . Aspergillus niger Introduction In 2010, there were more than 200 million cases of malaria and at least 655,000 deaths (World Health Organization 2011). Artemisinin (Fig. 1) 1 (qinghaosu), isolated from Artemisia annua L., is a sesquiterpene lactone endoperoxide (Klayman 1985). The structure of 1 was determined by X-ray analysis (Liu et al. 1979). Artemisinin and its derivatives are now in routine use for treatment of severe malaria because they can be used for combating multidrug-resistant Plasmodium falciparum strains of malaria that cannot be eliminated by classical quinoline and antifolate antibiotics. Artemisinin still has disadvantages of a high recrudescence rate and poor sol- ubility in water. So, it is important to find new and more effective antimalarial drugs by modifying the structure of artemisinin and its analogues through chemical and biological methods. Some studies on the structural modification of artemisinin by chemical and biological methods were reported (Gaur et al. 2014; Parshikov et al. 2004a, b, 2006; Zhan et al. 2002; Goswami et al. 2010; Acton 1999). Here, we report the biotransformation of 1 by Aspergillus niger VKM F-1119. Four products were obtained, among which two were identified as new compounds. These may supply novel bioactive antimalarial agents and precursors for synthesis of other new bioactive antimalarial drugs. Materials and methods General 1 H NMR (nuclear magnetic resonance) and 13 C NMR spectra were recorded in CDCl 3 (chloroform-d) on a Bruker AV400 operating at 400 and 100 MHz, respectively. Chemical shifts were reported in ppm ( δ) relative to tetramethylsilane (TMS) as an internal standard, and J values are in hertz. High-resolution mass spectra (HRMS) were ob- tained using a Micromass Q-Tof Micro with a lock spray source. The X-ray diffraction experiment for compound 2 was performed using a Bruker SMART CCD diffractometer. SMART (Bruker 2002) was used in data collection, and SAINT (Bruker 2002) was used in cell refinement and data Y. Zhan : P. Wei : Z. Chen School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, People’ s Republic of China Y. Zhan (*) : H. Liu : Y. Wu : J. S. Williamson Department of Medicinal Chemistry, University of Mississippi, University, MS 38677-1848, USA e-mail: zhanyulian@hotmail.com J. S. Williamson (*) Division of Extramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892-5475, USA e-mail: williamsonjs@mail.nih.gov Appl Microbiol Biotechnol (2015) 99:3443–3446 DOI 10.1007/s00253-015-6464-x