Yan, W. and Ge, H.M. and Wang, G. and Jiang, N. and Mei, Y.N. and Jiang, R. and Li, S.J. and Chen, C.J. and Jiao, R.H. and Xu, Q. and Ng, Seik Weng and Tan, R.X. (2014) Pictet-Spengler reaction-based biosynthetic machinery in fungi. Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490, 111 (51). pp. 18138-18143.
Full text not available from this repository.Abstract
The Pictet-Spengler (PS) reaction constructs plant alkaloids such as morphine and camptothecin, but it has not yet been noticed in the fungal kingdom. Here, a silent fungal Pictet-Spenglerase (FPS) gene of Chaetomium globosum 1C51 residing in Epinephelus drummondhayi guts is described and ascertained to be activable by 1-methyl-L-tryptophan (1-MT). The activated FPS expression enables the PS reaction between 1-MT and flavipin (fungal aldehyde) to form ``unnatural'' natural products with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase. A gene-implied enzyme inhibition (GIEI) strategy has been introduced to address the key steps for PS product diversifications. In aggregation, the work designs and validates an innovative approach that can activate the PS reaction-based fungal biosynthetic machinery to produce unpredictable compounds of unusual and novel structure valuable for new biology and biomedicine.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Pictet-Spengler reaction; FPS; Chaetomium globosum 1C51; GIEI |
| Subjects: | Q Science > Q Science (General) |
| Depositing User: | Dr Mohd Faizal Hamzah |
| Date Deposited: | 29 Dec 2015 01:55 |
| Last Modified: | 29 Dec 2015 01:55 |
| URI: | http://eprints.um.edu.my/id/eprint/15385 |
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