1,10/1,11-Cyclization catalyzed by diverged plant sesquiterpene synthases is dependent on a single residue.
Org Biomol Chem
; 19(30): 6650-6656, 2021 08 05.
Article
in English
| MEDLINE | ID: covidwho-1343477
ABSTRACT
The exquisite chemodiversity of terpenoids is the product of the large diverse terpene synthase (TPS) superfamily. Here, by using structural and phylogenetic analyses and site-directed mutagenesis, we identified a residue (Cys440 in Nicotiana tabacum 5-epi-aristolochene synthase) proximal to an ion-binding motif common to all TPSs and named the preNSE/DTE residue, which determines the product specificity of sesquiterpene synthases from different plant species. In sesquiterpene synthases catalyzing 1,10-cyclization (1,10-cyclases) of farnesyl diphosphate, mutation of the residue in both specific and promiscuous 1,10-cyclases from different lineages leads to the accumulation of monocyclic germacrene A-11-ol, which is "short-circuited" from complex cyclization cascades, suggesting a key role of this residue in generating the first common intermediate of 1,10-cyclization. Altering this residue in a specific 1,11-cyclase results in alternative 1,10-cyclization products. Moreover, the preNSE/DTE residue can be harnessed to engineer highly specific sesquiterpene synthases for an improved proportion of high-value terpenoids, such as patchoulol, a main constituent of several traditional Chinese medicines that could treat SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Alkyl and Aryl Transferases
/
Biocatalysis
Type of study:
Randomized controlled trials
Language:
English
Journal:
Org Biomol Chem
Journal subject:
Biochemistry
/
Chemistry
Year:
2021
Document Type:
Article
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