Title
Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis
Campus Units
Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
9-2016
Journal or Book Title
Metabolic Engineering
Volume
37
First Page
24
Last Page
34
DOI
10.1016/j.ymben.2016.04.001
Abstract
Diterpenes are widely distributed across many biological kingdoms, where they serve a diverse range of physiological functions, and some have significant industrial utility. Their biosynthesis involves class I diterpene synthases (DTSs), whose activity can be preceded by that of class II diterpene cyclases (DTCs). Here, a modular metabolic engineering system was used to examine the promiscuity of DTSs. Strikingly, both a bacterial and plant DTS were found to exhibit extreme promiscuity, reacting with all available precursors with orthogonal activity, producing an olefin or hydroxyl group, respectively. Such DTS promiscuity enables combinatorial biosynthesis, with remarkably high yields for these unoptimized non-native enzymatic combinations (up to 15 mg/L). Indeed, it was possible to readily characterize the 13 unknown products. Notably, 16 of the observed diterpenes were previously inaccessible, and these results provide biosynthetic routes that are further expected to enable assembly of more extended pathways to produce additionally elaborated ‘non-natural’ diterpenoids.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Owner
International Metabolic Engineering Society
Copyright Date
2016
Language
en
File Format
application/pdf
Recommended Citation
Jia, Meirong; Potter, Kevin C.; and Peters, Reuben J., "Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis" (2016). Biochemistry, Biophysics and Molecular Biology Publications. 268.
https://lib.dr.iastate.edu/bbmb_ag_pubs/268
Included in
Biochemistry Commons, Biophysics Commons, Molecular Biology Commons, Structural Biology Commons
Comments
This is a manuscript of an article published as Jia, Meirong, Kevin C. Potter, and Reuben J. Peters. "Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis." Metabolic engineering 37 (2016): 24-34. doi: 10.1016/j.ymben.2016.04.001. Posted with permission.