Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
iScience
2022 Mar 10;254:104030. doi: 10.1016/j.isci.2022.104030.
Show Gene links
Show Anatomy links
Unusual (2R,6R)-bicyclo[3.1.1]heptane ring construction in fungal α-trans-bergamotene biosynthesis.
Wen YH
,
Chen TJ
,
Jiang LY
,
Li L
,
Guo M
,
Peng Y
,
Chen JJ
,
Pei F
,
Yang JL
,
Wang RS
,
Gong T
,
Zhu P
.
???displayArticle.abstract???
Bergamotenes are bicyclo[3.1.1]heptane sesquiterpenes found abundantly in plants and fungi. Known bergamotene derivatives all possess (2S,6S)-bergamotene backbone. In this study, two (+)-α-trans-bergamotene derivatives (1 and 2) with unusual (2R,6R) configuration were isolated and elucidated from marine fungus Nectria sp. HLS206. The first (+)-α-trans-bergamotene synthase NsBERS was characterized using genome mining and heterologous expression-based strategies. Based on homology search, we characterized another (+)-α-trans-bergamotene synthase LsBERS from Lachnellula suecica and an (+)-α-bisabolol synthase BcBOS from Botrytis cinerea. We proposed that the cyclization mechanism of (+)-α-trans-bergamotene involved endo-anti cyclization of left-handed helix farnesyl pyrophosphate by (6R)-bisabolyl cation, which was supported by molecular docking. The biosynthesis-based volatiles (3-6) produced by heterologous fungal expression systems elicited significant electroantennographic responses of Helicoverpa armigera and Spodoptera frugiperda, respectively, suggesting their potential in biocontrol of these pests. This work enriches diversity of sesquiterpenoids and fungal sesquiterpene synthases, providing insight into the enzymatic mechanism of formation of enantiomeric sesquiterpenes.
Figure 1. Structure elucidation of compounds 1, 2 and 2′ isolated from the marine fungus Nectria sp. HLS206(A–C) (A) Structures of compounds 1, 2 and 2′; (B) Key COSY, HMBC and ROESY correlations of 1 and 2; (C) X-Ray ORTEP drawing of 1.
Figure 2. The sesquiterpenome of Nectria sp. HLS206(A and B) (A) Schematic representation of the nec and lach gene clusters and their amino acid sequence identity (The genes necD and lachB encode NsBERS and LsBERS, respectively); (B) The mining and identification of STSs in Nectria sp. HLS206. The n-dodecane layers of AN-nec04, AN-necD and AN-nec26 expressed strains were analyzed by GC-MS. The asterisks represent minor products of AN-nec26 and the triangle represents dodecanol at 10.35 min.
Figure 3. Phylogenetic analysis of fungal sesquiterpene synthasesFma-TC of UbiA superfamily was chosen as the outgroup. Branches are labeled with triangles representing the percentage of 1000 bootstrap replicates. The initial cyclization mechanism catalyzed by identified enzymes are indicated in square brackets. Hyp3 (1,8-cineole synthase) from Hypoxylon sp. in clade III is the first identified fungal monoterpene synthase and its mutants N136S and N136A can yield sesquiterpene products. TVY81921.1 corresponds to LachB in Figure 2A.
Figure 4. Heterologous expression of NsBERS-like STSs (NsBERS, TVY81921.1 and XP_001546971.2) in S. cerevisiae BJ5464(A) Schematic representation of the engineered sesquiterpenoid biosynthetic pathway in S. cerevisiae. The key enzymes HMGR and ERG20 were overexpressed to produce sufficient FPP for the production of sesquiterpenoids.(B) The function characterization of TVY81921.1 and XP_001546971.2. The n-octane layers of S. cerevisiae engineered strains were analyzed by GC-MS. The asterisks represent minor product of XP_001546971.2.
Figure 5. The proposed left-handed endo-anti cyclization mechanism of NsBERS, LsBERS and BcBOS(A) (2E,6E)-FPP; (B) (3R)-NPP; and (C) (+)-α-trans-bergamotene were docked into NsBERS model, while (D) (2E,6E)-FPP; (E) (3S)-NPP; and (F) (−)-α-trans-bergamotene were docked into LaBERS model. The crystal structure of (4S)-limonene synthase complex (PDB: 2ONH) was used as the template for homology modeling of LaBERS.
Figure 6. The EAG responses (mV) of Helicoverpa armigera and Spodoptera frugiperda were elicited by (+)-α-trans-bergamotene (3), (−)-trichoacorenol (4), (3R,6E)-nerolidol (5) and (+)-α-bisabolol (6)The EAG responses are represented as mean ± SEM.
Agger,
Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus.
2009, Pubmed
Agger,
Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus.
2009,
Pubmed
Bian,
Releasing the potential power of terpene synthases by a robust precursor supply platform.
2017,
Pubmed
Bian,
Metabolic Engineering-Based Rapid Characterization of a Sesquiterpene Cyclase and the Skeletons of Fusariumdiene and Fusagramineol from Fusarium graminearum.
2018,
Pubmed
Blin,
antiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification.
2017,
Pubmed
Brill,
Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products.
2017,
Pubmed
Brock,
Genetic dissection of sesquiterpene biosynthesis by Fusarium fujikuroi.
2013,
Pubmed
Chan,
Nerolidol: A Sesquiterpene Alcohol with Multi-Faceted Pharmacological and Biological Activities.
2016,
Pubmed
Christianson,
Unearthing the roots of the terpenome.
2008,
Pubmed
Christianson,
Structural and Chemical Biology of Terpenoid Cyclases.
2017,
Pubmed
Cistola,
Ionization behavior of aqueous short-chain carboxylic acids: a carbon-13 NMR study.
1982,
Pubmed
Croteau,
Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (-)-pinene cyclases from sage.
1989,
Pubmed
Dixit,
Chemical Control in the Battle against Fidelity in Promiscuous Natural Product Biosynthesis: The Case of Trichodiene Synthase.
2017,
Pubmed
Giroux,
Whole Genome Sequencing Resource of the European Larch Canker Pathogen Lachnellula willkommii for Molecular Diagnostic Marker Development.
2020,
Pubmed
Guo,
Odorant Receptors for Detecting Flowering Plant Cues Are Functionally Conserved across Moths and Butterflies.
2021,
Pubmed
Havlíčková,
(3R,6E)-nerolidol, a fertility-related volatile secreted by the queens of higher termites (Termitidae: Syntermitinae).
2019,
Pubmed
He,
Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases.
2020,
Pubmed
Jindal,
Revisiting sesquiterpene biosynthetic pathways leading to santalene and its analogues: a comprehensive mechanistic study.
2012,
Pubmed
Jones,
Sandalwood fragrance biosynthesis involves sesquiterpene synthases of both the terpene synthase (TPS)-a and TPS-b subfamilies, including santalene synthases.
2011,
Pubmed
Kampranis,
Rational conversion of substrate and product specificity in a Salvia monoterpene synthase: structural insights into the evolution of terpene synthase function.
2007,
Pubmed
Kanchiswamy,
Chemical diversity of microbial volatiles and their potential for plant growth and productivity.
2015,
Pubmed
Katoh,
MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform.
2002,
Pubmed
Kennedy,
Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis.
1999,
Pubmed
Kumar,
Structural Characterization of Early Michaelis Complexes in the Reaction Catalyzed by (+)-Limonene Synthase from Citrus sinensis Using Fluorinated Substrate Analogues.
2017,
Pubmed
Kumar,
MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.
2016,
Pubmed
Landmann,
Cloning and functional characterization of three terpene synthases from lavender (Lavandula angustifolia).
2007,
Pubmed
Laurini,
Direct Identification of α-Bisabolol Enantiomers in an Essential Oil Using a Combined Ion Mobility-Mass Spectrometry/Quantum Chemistry Approach.
2020,
Pubmed
Li,
PIG3 promotes NSCLC cell mitotic progression and is associated with poor prognosis of NSCLC patients.
2017,
Pubmed
Lin,
The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.
2013,
Pubmed
Lopez-Gallego,
Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers.
2010,
Pubmed
Lu,
CDD/SPARCLE: the conserved domain database in 2020.
2020,
Pubmed
Miller,
Sesquiterpene synthases: passive catalysts or active players?
2012,
Pubmed
Muangphrom,
Identification and characterization of (+)-α-bisabolol and 7-epi-silphiperfol-5-ene synthases from Artemisia abrotanum.
2019,
Pubmed
Muangphrom,
Functional Analysis of Amorpha-4,11-Diene Synthase (ADS) Homologs from Non-Artemisinin-Producing Artemisia Species: The Discovery of Novel Koidzumiol and (+)-α-Bisabolol Synthases.
2016,
Pubmed
Oh,
Massarinolins A-C: new bioactive sesquiterpenoids from the aquatic fungus massarina tunicata.
1999,
Pubmed
Ohashi,
SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis.
2017,
Pubmed
Peng,
Mycotoxin Ochratoxin A-induced cell death and changes in oxidative metabolism of Arabidopsis thaliana.
2010,
Pubmed
Peralta-Yahya,
Identification and microbial production of a terpene-based advanced biofuel.
2011,
Pubmed
Porté,
Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase PIG3.
2009,
Pubmed
Quin,
Traversing the fungal terpenome.
2014,
Pubmed
Rinkel,
Mechanistic Studies on Trichoacorenol Synthase from Amycolatopsis benzoatilytica.
2020,
Pubmed
Sallaud,
A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in the wild tomato Solanum habrochaites.
2009,
Pubmed
Schnee,
The maize gene terpene synthase 1 encodes a sesquiterpene synthase catalyzing the formation of (E)-beta-farnesene, (E)-nerolidol, and (E,E)-farnesol after herbivore damage.
2002,
Pubmed
Shaw,
Identification of a fungal 1,8-cineole synthase from Hypoxylon sp. with specificity determinants in common with the plant synthases.
2015,
Pubmed
Tantillo,
Biosynthesis via carbocations: theoretical studies on terpene formation.
2011,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Van Kan,
A gapless genome sequence of the fungus Botrytis cinerea.
2017,
Pubmed
Wang,
Purpurolide A, 5/5/5 Spirocyclic Sesquiterpene Lactone in Nature from the Endophytic Fungus Penicillium purpurogenum.
2018,
Pubmed
Waterhouse,
SWISS-MODEL: homology modelling of protein structures and complexes.
2018,
Pubmed
Wawrzyn,
Draft genome of Omphalotus olearius provides a predictive framework for sesquiterpenoid natural product biosynthesis in Basidiomycota.
2012,
Pubmed
Whittington,
Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase.
2002,
Pubmed
Williams,
Tipping the balance: Sclerotinia sclerotiorum secreted oxalic acid suppresses host defenses by manipulating the host redox environment.
2011,
Pubmed
Yan,
Complexity and Diversity Generation in the Biosynthesis of Fumiquinazoline-Related Peptidyl Alkaloids.
2019,
Pubmed
Yan,
Recent developments in self-resistance gene directed natural product discovery.
2020,
Pubmed
Yan,
Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.
2018,
Pubmed
Ying,
Bergamotane Sesquiterpenes with Alpha-Glucosidase Inhibitory Activity from the Plant Pathogenic Fungus Penicillium expansum.
2017,
Pubmed
Zhang,
Agrocybe aegerita Serves As a Gateway for Identifying Sesquiterpene Biosynthetic Enzymes in Higher Fungi.
2020,
Pubmed
Zhou,
Tissue-Specific Emission of (E)-α-Bergamotene Helps Resolve the Dilemma When Pollinators Are Also Herbivores.
2017,
Pubmed
