scholarly journals Engineering of Ancestors as a Tool to Elucidate Structure, Mechanism, and Specificity of Extant Terpene Cyclase

2021 ◽  
Author(s):  
Karen Schriever ◽  
Patricia Saenz-Mendez ◽  
Reshma Srilakshmi Rudraraju ◽  
Natalie M. Hendrikse ◽  
Elton P. Hudson ◽  
...  
Keyword(s):  
Terpene Cyclase

A putative terpene cyclase, vir4, is responsible for the biosynthesis of volatile terpene compounds in the biocontrol fungus Trichoderma virens

2013 ◽  
Vol 56 ◽  
pp. 67-77 ◽  
Author(s):  
Frankie K. Crutcher ◽  
Alexandra Parich ◽  
Rainer Schuhmacher ◽  
Prasun K. Mukherjee ◽  
Susanne Zeilinger ◽  
...  
Keyword(s):  
Trichoderma Virens ◽  
Terpene Cyclase ◽  
Volatile Terpene

Substrate Pre-Folding and Water Molecule Organization Matters for Terpene Cyclase Catalyzed Conversion of Unnatural Substrates

2016 ◽  
Vol 1 (13) ◽  
pp. 3589-3593 ◽  
Author(s):  
Stephan C. Hammer ◽  
Per-Olof Syrén ◽  
Bernhard Hauer
Keyword(s):  
Water Molecule ◽  
Terpene Cyclase

scholarly journals Silent catalytic promiscuity in the high-fidelity terpene cyclase δ-cadinene synthase

2019 ◽  
Vol 17 (5) ◽  
pp. 1206-1214 ◽  
Author(s):  
Marianna Loizzi ◽  
David J. Miller ◽  
Rudolf K. Allemann
Keyword(s):  
High Fidelity ◽  
Catalytic Promiscuity ◽  
Terpene Cyclase

Aza-analogues of carbocations inhibit δ-cadinene synthase: 1,6-cyclisation.

scholarly journals Protonation-Initiated Cyclization by a Class II Terpene Cyclase Assisted by Tunneling

ChemBioChem ◽  
2017 ◽  
Vol 18 (23) ◽  
pp. 2301-2305 ◽  
Author(s):  
Adam Eriksson ◽  
Charlotte Kürten ◽  
Per-Olof Syrén
Keyword(s):  
Class Ii ◽  
Terpene Cyclase

scholarly journals Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3811
Author(s):  
Javier E. Barúa ◽  
Mercedes de la Cruz ◽  
Nuria de Pedro ◽  
Bastien Cautain ◽  
Rosa Hermosa ◽  
...  
Keyword(s):  
Human Hepatocytes ◽  
Bioactive Molecules ◽  
Cytotoxic Activities ◽  
Terpene Cyclase ◽  
Trichodiene Synthase ◽  
Specific Step ◽  
Ic50 Values ◽  
Selective Antimicrobial Activity ◽  
Tumorigenic Cell Line ◽  
Mcf 7

Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC50 values of 2 μg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes).

Identification of Chimeric αβγ Diterpene Synthases Possessing both Type II Terpene Cyclase and Prenyltransferase Activities

ChemBioChem ◽  
2017 ◽  
Vol 18 (21) ◽  
pp. 2104-2109 ◽  
Author(s):  
Takaaki Mitsuhashi ◽  
Masahiro Okada ◽  
Ikuro Abe
Keyword(s):  
Type Ii ◽  
Terpene Cyclase ◽  
Diterpene Synthases

scholarly journals Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

2017 ◽  
Vol 13 ◽  
pp. 2458-2465 ◽  
Author(s):  
Xinli Pan ◽  
Nicole Domin ◽  
Sebastian Schieferdecker ◽  
Hirokazu Kage ◽  
Martin Roth ◽  
...  
Keyword(s):  
Large Scale ◽  
Biosynthetic Pathway ◽  
Isotope Labeling ◽  
Molecular Architecture ◽  
Methylerythritol Phosphate Pathway ◽  
Methylerythritol Phosphate ◽  
Isotope Pattern ◽  
Terpene Cyclase ◽  
Mass Shifts ◽  
Characteristic Mass

The genome of the predatory bacterium Herpetosiphon aurantiacus 114-95T harbors a number of biosynthesis genes, including four terpene cyclase genes. To identify the terpenes biosynthesized from H. aurantiacus 114-95T, we fed the strain with 13C-labeled glucose and, subsequently, searched for characteristic mass shifts in its metabolome. This approach led to the discovery of a new natural product, of which the isotope pattern is indicative for a diterpene originating from the methylerythritol phosphate pathway. After large-scale fermentation of H. aurantiacus 114-95T, the putative diterpene was isolated in sufficient quantity to enable NMR-based structure elucidation. The compound, for which the name herpetopanone is proposed, features a rare octahydro-1H-indenyl skeleton. Herpetopanone bears resemblance to cadinane-type sesquiterpenes from plants, but is structurally entirely unprecedented in bacteria. Based on its molecular architecture, a possible biosynthetic pathway is postulated.

scholarly journals The ABCs (and Ds) of Class I Terpene Cyclase (αC), Trans- Head-to-Tail (αHT) and Head-to-Head (αHH) Prenyltransferase Structures and Mechanisms of Action

2019 ◽  
Author(s):  
Chun-Chi Chen ◽  
Satish Malwal ◽  
Xu Han ◽  
Weidong Liu ◽  
Lixin Ma ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Mechanisms Of Action ◽  
Farnesyl Diphosphate ◽  
Class I ◽  
General Interest ◽  
Santalum Album ◽  
Conserved Residues ◽  
Terpene Cyclase ◽  
Sequential Mechanism ◽  
Bond Network

We report the structures of the terpene cyclases <i>Santalum album</i> L. sesquisabinene synthases 1 and 2 and of santalene synthase, in apo forms, and with the sesquisabinene synthases, bound to either farnesyl diphosphate (FPP), farnesyl S-thiolo-diphosphate, FPP containing a POP bridging O-to-CCl<sub>2</sub> substitution, or to sabinene, leading to a sequential mechanism for substrate binding and catalysis. We trapped early pre-catalytic inactive open forms that show how ligands initially bind to the apo-proteins, then when the pocket closes, catalysis can proceed. We also show that there are strong structural similarities between the most highly conserved residues in class I cyclases and those in head-to-tail (aHT) trans-prenyl transferases—outside the well-known DDXXD-like and NSE/DTE-like domains. In the aHT prenyltransferases there is a highly conserved Thr>Gln>Asp>Tyr motif and in the cyclases, a similar Thr>Arg>Asp>Tyr domain, these residues forming very similar, extended H-bond networks (rmsd ~1.4 Å) that are involved in catalysis, leading to the proposal that there are 3 key domains in both the cyclases and the aHT prenyltransferases: The AC-domain that binds MgA and MgC; the B domain that binds MgB and leads to pocket closure, ionization, and condensation or cyclization; and the D-domain H-bond network, involved in H<sup>+</sup> elimination. In aHH prenyltransferases the overall folds and MgABC motifs are similar to those found in the cyclase and aHT proteins, but the full Thr>Arg/Gln>Asp>Tyr domain is absent and instead there are Tyr/Asp or Tyr/Glu residues that bind to MgC and are highly conserved. Overall, the results are of general interest since they show unexpected similarities between the enzymes that produce the most diverse molecules on Earth: aHT and aHH prenyltransferases, and terpenoid cyclases.

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