|
|||||
|
|
Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues |
|
| Authors: | Woncheol Kim Dr Dongho Lee Dr Seong Su Hong Dr Zhu Na Jin Chul Shin Su Heun Roh Cheng‐Zhu Wu Oksik Choi Kyeong Lee Dr Yue‐Mao Shen Dr Sang‐Gi Paik Dr Jung Joon Lee Dr Young‐Soo Hong Dr |
| Affiliation: | 1. Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305‐806 (Korea), Fax: (+82)?42‐860‐4595;2. Chungnam National University, Daejeon 305‐764 (Korea);3. School of Life Sciences and Biotechnology, Korea University, Seoul 136‐713 (Korea);4. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204 (China);5. Graduate University of Chinese Academy of Sciences, Beijing 100049 (China) |
| Abstract: | Tailor made : We report the rational biosynthesis of C15 hydroxylated non‐quinone geldanamycin analogues by site‐directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post‐PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound.  |
| Keywords: | biosynthesis geldanamycin natural products polyketides site‐directed mutagenesis |