Search

Promoting endogenous neurogenesis for brain repair is emerging as a promising strategy to mitigate the functional impairments associated with various neurological disorders characterized by neuronal death. Diterpenes featuring tigliane, ingenane, jatrophane and lathyrane skeletons, frequently found in Euphorbia plant species, are known protein kinase C (PKC) activators and exhibit a wide variety of pharmacological properties, including the stimulation of neurogenesis. Microbial transformation of these diterpenes represents a green and sustainable methodology that offers a hitherto little explored approach to obtaining novel derivatives and exploring structure-activity relationships. In the present study, we report the biotransformation of euphoboetirane A (4) and epoxyboetirane A (5), two lathyrane diterpenoids isolated from Euphorbia boetica, by Mucor circinelloides MC NRRL3631. Our findings revealed the production of nine biotransformation products (6-14), including jatrophane derivatives originated through an unprecedented rearrangement from the parent lathyranes. The chemical structures and absolute configurations of the new compounds were elucidated through comprehensive analysis using NMR and ECD spectroscopy, as well as MS. The study evaluated how principal metabolites and their derivatives affect TGFα and NRG1 release, as well as their potential to promote proliferation or differentiation in cultures of NSC isolated from the SVZ of adult mice. In order to shed some light on the mechanisms underlying the ability of 12 as a neurogenic compound, the interactions of selected compounds with PKC δ-C1B were analyzed through molecular docking and molecular dynamics. Based on these, it clearly appears that the ability of compound 12 to form both acceptor and donor hydrogen bonds with certain amino acid residues in the enzyme pocket leads to a higher affinity compound-PKC complex, which correlates with the observed biological activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Botrytis cinerea has high potential for the production of specialized metabolites. The recent resequencing of the genome of the B05.10 strain using PacBio technology and the resulting update of the Ensembl Fungi (2017) database in the genome sequence have been instrumental in identifying new genes that could be involved in secondary metabolism. Thus, a new sesquiterpene cyclase (STC) coding gene (Bcstc7) has been included in the gene list from this phytopathogenic fungus. We recently constructed the null and complement transformants in STC7 which enabled us to functionally characterize this STC. Deletion of the Bcstc7 gene abolished (+)-4-epi-eremophilenol biosynthesis, and could then be re-established by complementing the null mutant with the Bcstc7 gene. Chemical analysis of the complemented transformant suggests that STC7 is the principal enzyme responsible for the key cyclization step of farnesyl diphosphate (FDP) to (+)-4-epi-eremophil-9-en-11-ols. A thorough analysis of the metabolites produced by two wild-type strains, B05.10 and UCA992, and the complemented mutant compl ΔBcstc7 niaD , revealed the isolation and structural characterization of six 11,12,13-tri-nor-eremophilene derivatives, in addition to a large number of known eremophilen-11-ol derivatives. The structural characterization was carried out by extensive spectroscopic techniques. The biosynthesis of these compounds is explained by a retroaldol reaction or by dehydration and oxidative cleavage of C11-C13 carbons. This is the first time that this interesting family of degraded eremophilenols has been isolated from the phytopathogenous fungus B. cinerea., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Botrytis cinerea is a necrotrophic fungal pathogen that affects a total of 586 genera representing approximately 1400 plant species. This pathogen produces two families of phytotoxins involved in its infection process i.e. botrydial and its relatives, and botcinic and botcineric acids and their relatives, botcinins. The botrydial biosynthetic cluster consists of seven genes, where the gene BcBOT4 encodes a cytochrome P450 monooxygenase that was shown to catalyse regio- and stereospecific hydroxylation at position C-4 of the presilphiperfolan-8-β-ol skeleton. The null mutant bcbot4Δ halted the production of botrydial and its derivatives, and instead accumulated tricyclic presilphiperfolane alcohol and overproduced a significant number of polyketides. A detailed study of the bcbot4Δ mutant led us to the isolation and characterization of five undescribed polyketides, three derived from botcinic and botcineric acids (botcinins H, I, J), one derived from the initial pentaketide (botcinin K), and one cinbotolide derivative (cinbotolide D). Botcinins are tetra-methylated tetraketides biosynthesized by the sequential assembly of a pentaketide (C10) based on an acetate primer unit which is lost through a retro-Claisen type C-C bond cleavage. The structural characterization of botcinin K showed a basic chemical structure corresponding to a botcinin (C14) derivative obtained directly from the original per-methylated pentaketide leading to the biosynthesis of botrylactone and other botcinins, confirming the previously proposed biosynthetic route., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The reaction mechanism of the intramolecular [2 + 2] cycloaddition from a jatrophane precursor to the gaditanane skeleton, an unprecedented 5/6/4/6-fused tetracyclic ring framework recently isolated from Euphorbia spp., was studied using the bond reactivity indices approach. Furthermore, six diterpenoids, including three undescribed jatrophanes isolated from E. gaditana Coss, were described. The structures of these compounds were deduced by a combination of 2D NMR spectroscopy and ECD data analysis., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A thorough study of the fermentation broth of three strains of Botrytis cinerea which were grown on a modified Czapek-Dox medium supplemented with 5 ppm copper sulphate, yielded five undescribed metabolites. These metabolites possessed a sesquiterpenoid (+)-4-epi-eremophil-9-ene carbon skeleton which was enantiomeric to that of the phytoalexin, capsidiol. The isolation of these metabolites when the fungus was stressed, suggests that they may be potential effectors used by B. cinerea to circumvent plant chemical defences against phytopathogenic fungi. The biosynthesis of these compounds has been studied using 2 H and 13 C labelled acetate., (Copyright © 2018. Published by Elsevier Ltd.)

The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy, referred to as HAART. HIV-1 reservoirs are long-lived resting CD4+ memory cells containing the virus latently integrated. Since the HIV-1 reservoirs are not targeted by HAART, reactivation therapy has been suggested to purge viral latency. Bioassay-guided study of an ethyl acetate extract of Euphorbia laurifolia afforded two isomeric diterpenes that showed differential activity over HIV-1 reactivation. A previously reported compound was isolated too from Euphorbia lactea. This compound showed a potent HIV-1 reactivating effect. Bioassays results showed that HIV-1 reactivation activity is influenced by distinct structural characteristics., (2009 Elsevier Ltd. All rights reserved.)

Bioassay-guided fractionation of ethanolic extract from the wood of Juniperus lucayana afforded three sesquiterpenes named 3-hydroxypseudowiddran-6(7)-en-4-ol (1), 15-hydroxyallo-cedrol (2) and 12-hydroxywiddrol (3) together with six known sesquiterpenes (4-9) and two known flavonoids (10 and 11). Their structures were established on the basis of comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry. The structures of compounds were identified as 1alpha,4beta,11alpha,11beta-tetramethylbicyclo[5,4,0]undec-6(7)-en-3alpha, 4alpha-diol (1), 4beta-hydroxymethyl-5,5,9beta-trimethyltricyclo[4.3.0.2(1.4)]undecan-3alpha-ol (2) and 4beta-hydroxymethyl-7alpha,11alpha,11beta-trimethylbicyclo [5.4.0]undec-1-en-4alpha-ol (3). The major compounds isolated were evaluated for their antifungal activity against Botrytis cinerea. Widdrol (7) was the most active, reaching the 71% inhibition level on mycelial growth after 6 days.