Abstract
Ordered polycyclization catalyzed by oxidosqualene synthases (OSCs) morph a common linear precursor into structurally complex and diverse triterpene scaffolds with varied bioactivities. We identified three OSCs from Iris tectorum. ItOSC2 is a rare multifunctional α-amyrin synthase. Sequence comparisons, site-directed mutagenesis and multiscale simulations revealed that three spatially clustered residues, Y531/L256/L258 form an unusual Y-LL triad at the active site, replacing the highly conserved W-xY triad occurring in other amyrin synthases. The discovery of this unprecedented active site architecture in ItOSC2 underscores the plasticity of terpene cyclase catalytic mechanisms and opens new avenues for protein engineering towards custom designed OSCs.
| Original language | English |
|---|---|
| Pages (from-to) | 9515-9520 |
| Journal | ACS Catalysis |
| Volume | 10 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - 21 Aug 2020 |
| MoE publication type | A1 Journal article-refereed |
Funding
Work in the authors’ laboratories was supported by grants from the National Natural Science Foundation of China (No.81874333 to L.D., and No.21773313 to R.W.); the Science and Technology Program of Guangzhou, China (No.2018-1002-SF-0437 to L.D.); the Guangdong Natural Science Funds for Distinguished Young Scholars (2016A030306038 to R.W.); the National Key Research and Development Program of China (No. 2017YFE0191500 to S.W); the USDA National Institute of Food and Agriculture (Hatch project ARZT-1361640-H12-224 to I.M.); the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary (NKFIH-1150-6/2019 to I.M.); and the U.S. National Institutes of Health (NIGMS 5R01GM114418 to I.M).
Keywords
- enzyme catalysis
- enzyme promiscuity
- oxidosqualene cyclase
- QM/MM
- triterpene