Abstract
Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single-residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions that are presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests an alternative interpretation of previous results and potential routes toward reengineering terpene synthase activity more generally.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8867-8871 |
| Number of pages | 5 |
| Journal | ACS Catalysis |
| Volume | 9 |
| Issue number | 10 |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- acid-base catalysis
- biosynthesis
- enzymology
- natural products
- terpene synthases
ASJC Scopus subject areas
- Catalysis
- Chemistry(all)
Cite this
Switching on a Nontraditional Enzymatic Base - Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum. / Jia, Meirong; Zhang, Yue; Siegel, Justin B.; Tantillo, Dean J.; Peters, Reuben J.
In: ACS Catalysis, Vol. 9, No. 10, 01.01.2019, p. 8867-8871.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Switching on a Nontraditional Enzymatic Base - Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum
AU - Jia, Meirong
AU - Zhang, Yue
AU - Siegel, Justin B.
AU - Tantillo, Dean J.
AU - Peters, Reuben J.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single-residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions that are presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests an alternative interpretation of previous results and potential routes toward reengineering terpene synthase activity more generally.
AB - Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single-residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions that are presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests an alternative interpretation of previous results and potential routes toward reengineering terpene synthase activity more generally.
KW - acid-base catalysis
KW - biosynthesis
KW - enzymology
KW - natural products
KW - terpene synthases
UR - http://www.scopus.com/inward/record.url?scp=85072599774&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072599774&partnerID=8YFLogxK
U2 - 10.1021/acscatal.9b02783
DO - 10.1021/acscatal.9b02783
M3 - Article
AN - SCOPUS:85072599774
VL - 9
SP - 8867
EP - 8871
JO - ACS Catalysis
JF - ACS Catalysis
SN - 2155-5435
IS - 10
ER -