Catalytic Bases and Stereocontrol in Lamiaceae Class II Diterpene Cyclases
| Autor: | Reuben J. Peters, Samuel Schulte, Cody Lemke, Kevin C. Potter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
Models Molecular Stereochemistry Stereoisomerism Salvia miltiorrhiza Carbocation 01 natural sciences Biochemistry Article Substrate Specificity chemistry.chemical_compound Deprotonation Biosynthesis Plant Growth Regulators Plant Proteins chemistry.chemical_classification Alkyl and Aryl Transferases Lamiaceae ATP synthase biology 010405 organic chemistry Chemistry 0104 chemical sciences Biosynthetic Pathways Enzyme biology.protein Enantiomer Diterpene Diterpenes 010606 plant biology & botany |
| Popis: | Plants from the widespread Lamiaceae family produce many labdane-related diterpenoids, a number of which serve medicinal roles, and whose biosynthesis is initiated by class II diterpene cyclases (DTCs). These enzymes utilize a general acid-base catalyzed cyclo-isomerization reaction to produce various stereoisomers of the eponymous labdaenyl carbocation intermediate, which can then undergo rearrangement and/or the addition of water prior to terminating deprotonation. Identification of the pair of residues that cooperatively serve as the catalytic base in the DTCs that produce ent-copalyl diphosphate (CPP) required for gibberellin phytohormone biosynthesis in all vascular plants has led to insight into the addition of water as well as rearrangement. Lamiaceae plants generally contain an additional DTC that produces the enantiomeric normal CPP, as well as others that yield hydroxylated products derived from the addition of water. Here the catalytic base in these DTCs was investigated. Notably, changing two adjacent residues that seem to serve as the catalytic base in the normal CPP synthase from Salvia miltiorrhiza (SmCPS) to the residues found in the closely related perigrinol diphosphate synthase from Marrubium vulgare (MvPPS), which produces a partially rearranged and hydroxylated product derived from the distinct syn stereoisomer of labdaenyl(+), altered product outcome in an unexpected fashion. Specifically, the relevant SmCPS:H315N/T316V double mutant produces terpentedienyl diphosphate, which is derived from complete substituent rearrangement of syn rather than normal labdaenyl(+). Accordingly, alteration of the residues that normally serve as the catalytic base surprisingly can impact stereo-control. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|