Heterologous Biosynthesis of Fungal Indole Sesquiterpene Sespendole |
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| Authors: | Kosei Kudo Dr. Chengwei Liu Tomoyuki Matsumoto Dr. Atsushi Minami Dr. Taro Ozaki Prof. Dr. Hiroaki Toshima Prof. Dr. Katsuya Gomi Prof. Dr. Hideaki Oikawa |
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| Affiliation: | 1. Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, Japan;2. Department of Bioresource Science, College of Agriculture, Ibaraki University, Inashiki, Ibaraki, Japan;3. Graduate School of Agricultural Science, Tohoku University, Sendai, Japan |
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| Abstract: | Indole sesquiterpene sespendole, which has been isolated from the filamentous fungus Pseudobotrytis terrestris FKA‐25, is a specific inhibitor of lipid droplet synthesis in mouse macrophages. The biosynthetic pathway that involves genes encoding six enzymes (spdEMBQHJ) was elucidated through heterologous expression of spd genes in Aspergillus oryzae, biotransformation experiments, and in vitro enzymatic reactions with a recombinant protein, thereby revealing the mechanism underlying the characteristic modification on the indole ring, catalyzed by a set of prenyltransferase (SpdE)/cytochrome P450 (SpdJ) enzymes. Functional analysis of the homologous genes encoding these enzymes involved in the biosynthesis of lolitrem allowed a biosynthetic pathway for the bicyclic ring skeleton fused to the indole ring to be proposed. |
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| Keywords: | biosynthesis gene sequencing enzymes natural products terpenoids |
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