9VSI
The crystal structure of the germacrene A synthase FpGAS-T169F mutant in complex with beta-farnesene
This is a non-PDB format compatible entry.
Summary for 9VSI
| Entry DOI | 10.2210/pdb9vsi/pdb |
| Descriptor | Terpene synthase, MAGNESIUM ION, PYROPHOSPHATE 2-, ... (5 entities in total) |
| Functional Keywords | germacrene a synthase, lyase |
| Biological source | Fusarium poae |
| Total number of polymer chains | 1 |
| Total formula weight | 36518.18 |
| Authors | |
| Primary citation | Dong, S.,Liu, H.,Liao, W.,Chen, X.,Cui, T.,Zhang, R.,Wang, Q.,Han, Y.,Wang, L.,Men, X.,Zhang, H. Reprogramming product selectivity and activity in promiscuous terpene synthases via substrate conformation engineering. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Terpenoids are structurally diverse natural products with broad applications, yet their biosynthesis is often constrained by the low catalytic efficiency and poor product selectivity of terpene synthases (TPSs). Simultaneously enhancing product specificity and catalytic performance remains a major challenge in TPS engineering. Here, we elucidate the regio- and stereoselectivity of a fungal germacrene A synthase, which catalyzes the 1,10-cyclization of farnesyl diphosphate to form a central sesquiterpene intermediate. The side-chain volume of a non-catalytic residue (T169) adjacent to the substrate pocket modulates substrate-binding conformations, thereby redirecting the carbocation cascade and reshaping the product profile. Mechanism-guided pocket engineering further yielded terpene synthase variants with altered product specificity. Notably, one variant increased (+)-germacrene A production in Escherichia coli by 24.3-fold, reaching 15.8 g L⁻¹ in a bioreactor-the highest titer reported in this host to the best of our knowledge. These results provide mechanistic insight into substrate-conformation-mediated reprogramming of TPS specificity, highlighting a promising strategy for the development of high-performance terpenoid biocatalysts. PubMed: 42816480DOI: 10.1038/s41467-026-77224-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.43 Å) |
Structure validation
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