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The aim of this study is to make analogues of artemisinin using microbial transformation and evaluate their in vitro antimalarial activity. A panel of microorganisms were screened for biotransformation of artemisinin (<jats:bold>1<\/jats:bold>). The biotransformation products were extracted, purified and isolated using silica gel column chromatography and semi-preparative\u00a0HPLC. Spectroscopic methods including LC-HRMS, GC\u2013MS, FT-IR, 1D and 2D NMR were used to elucidate the structure of the artemisinin\u00a0metabolites.<jats:sup>1<\/jats:sup>H NMR spectroscopy was further used to study the time-course biotransformation. The antiplasmodial activity (IC<jats:sub>50<\/jats:sub>) of the biotransformation products of <jats:bold>1<\/jats:bold> against intraerythrocytic cultures of <jats:italic>Plasmodium falciparum<\/jats:italic> were determined using bioluminescence assays. A filamentous fungus <jats:italic>Aspergillus niger<\/jats:italic> CICC 2487 was found to possess the best efficiency to convert artemisinin (<jats:bold>1<\/jats:bold>) to a novel derivative, 4-methoxy-9,10-dimethyloctahydrofuro-(3,2-i)-isochromen-11(4H)-one (<jats:bold>2<\/jats:bold>) via ring rearrangement and further degradation, along with three known derivatives, compound (<jats:bold>3<\/jats:bold>), deoxyartemisinin (<jats:bold>4<\/jats:bold>) and 3-hydroxy-deoxyartemisinin (<jats:bold>5<\/jats:bold>). Kinetic study of the biotransformation of artemisinin indicated the formation of artemisinin G as a key intermediate which could be hydrolyzed and methylated to form the new compound <jats:bold>2<\/jats:bold>. Our study shows that the anti-plasmodial potency of compounds <jats:bold>2<\/jats:bold>, <jats:bold>3, 4<\/jats:bold> and <jats:bold>5<\/jats:bold> were ablated compared to <jats:bold>1,<\/jats:bold> which attributed to the loss of the unique peroxide bridge in artemisinin (<jats:bold>1)<\/jats:bold>. This is the first report of microbial degradation and ring rearrangement of artemisinin with subsequent hydrolysis and methoxylation by <jats:italic>A.niger.<\/jats:italic><\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key points<\/jats:title>\n                <jats:p>\u2022 <jats:italic>Aspergillus niger CICC 2487 was found to be efficient for biotransformation of artemisinin<\/jats:italic><\/jats:p>\n                <jats:p>\u2022 <jats:italic>A novel and unusual artemisinin derivative was isolated and elucidated<\/jats:italic><\/jats:p>\n                <jats:p>\u2022 The\u00a0<jats:italic>peroxide bridge in artemisinin is crucial for its high antimalarial potency<\/jats:italic><\/jats:p>\n                <jats:p>\u2022 <jats:italic>The pathway of biotransformation involves the formation of artemisinin G as a key intermediate<\/jats:italic><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00253-022-11888-0","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T01:02:34Z","timestamp":1648688554000},"page":"2433-2444","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biotransformation of artemisinin to a novel derivative via ring rearrangement by Aspergillus niger"],"prefix":"10.1007","volume":"106","author":[{"given":"Jiaer","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Mobley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Woodfine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Drijfhout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Horrocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Dong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-6068","authenticated-orcid":false,"given":"Wen-Wu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"5","key":"11888_CR1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2174\/0929867306666220320215539","volume":"6","author":"EA Abourashed","year":"1999","unstructured":"Abourashed EA, Clark AM, Hufford CD (1999) Microbial models of mammalian metabolism of xenobiotics: An updated review. 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