- 【Updated on May 12, 2025】 Integration of CiNii Dissertations and CiNii Books into CiNii Research
- Trial version of CiNii Research Knowledge Graph Search feature is available on CiNii Labs
- Suspension and deletion of data provided by Nikkei BP
- Regarding the recording of “Research Data” and “Evidence Data”
Toward Engineered Biosynthesis of Drugs in Human Cells
-
- Shinya Matsuda
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Yuta Tsunematsu
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Takuma Matsushita
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Yuji Ogata
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Shihomi Hachiya
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Shinji Kishimoto
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Noriyuki Miyoshi
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
-
- Kenji Watanabe
- Department of Pharmaceutical Sciences University of Shizuoka Shizuoka 422-8526 Japan
Search this article
Description
<jats:title>Abstract</jats:title><jats:p>Biosynthetic genes are not only responsible for the formation of bioactive substances but also suited for other applications including gene therapy. To test the feasibility of human cells producing antibiotics in situ when provided with a heterologous biosynthetic gene, we focused on cytochrome P450, the class of enzymes important in conferring bioactivity to natural product precursors. We selected Fma‐P450 that plays a central role in the fumagillin antimicrobial biosynthesis in <jats:italic>Aspergillus fumigatus</jats:italic> to examine fungal metabolite production by HeLa cells that express <jats:italic>fma‐P450</jats:italic> heterologously. Here we show that HeLa cells harboring <jats:italic>fma‐P450</jats:italic> can biosynthesize 5‐hydroxyl‐β‐<jats:italic>trans</jats:italic>‐bergamoten and cytotoxic 5‐<jats:italic>epi</jats:italic>‐demethoxyfumagillol when supplemented with the nontoxic precursor β‐<jats:italic>trans</jats:italic>‐bergamotene. While the production level was insufficient to effect cell death, we demonstrate that programming human cells to autogenerate antibiotics by introducing a heterologous biosynthetic gene is feasible.</jats:p>
Journal
-
- ChemBioChem
-
ChemBioChem 23 (4), 2021-12-29
Wiley
