Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains

Abstract

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Although diterpenoid substrates usually exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of Fusarium oxysporum (a fungus isolated from the rhizosphere of Senna spectabilis) and Myrothecium verrucaria (an endophyte) to transform halimane (1) and labdane (2) acids isolated from Hymenaea stigonocarpa (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl and carboxy analogues. Incubation of 1 with F. oxysporum afforded 2-oxo-derivative (3), while bioconversion with M. verrucaria provided 18,19-dihydroxy (4), 18-formyl (5) and 18-carboxy (6) bioproducts. Transformation of substrate 2 mediated by F. oxysporum produced a 7α-hydroxy (7) derivative, while M. verrucaria yielded 7α- (7) and 3β-hydroxy (8) metabolites. Unlike F. oxysporum, which showed a preference to transform ring B, M. verrucaria exhibited the ability to hydroxylate both rings A and B from substrate 2. Additionally, compounds 1–8 were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay.

An Overview of Biotransformation and Toxicity of Diterpenes

“…The microbial transformation of the halimane diterpene (+)-(4 R ,5 S ,8 R ,9 S )-18-hydroxy- ent -halima-1(10),13-( E )-dien-15-oic acid (compound 9 in Figure 11 ) and the labdane (+)-(5 S ,8 S ,9 R ,10 S )-lab-13-en-8β-ol-15-oic acid (compound 10 in Figure 11 ) by Fusarium oxysporum and Myrothecium verrucaria afforded hydroxyl, oxo, formyl, and carboxy derivatives (compounds 9.1 – 9.4 , 10.1 and 10.2 , Figure 11 ) [ 55 ]. F. oxysporum showed preference to modify ring B from substrate 10 , while M. verrucaria was able to transform both rings A and B.…”

“… Diterpenoids 9 and 10 and their derivatives obtained by Fusarium oxysporum and Myrothecium verrucaria biotransformation [ 55 ]. …”

Isolation of Three New Diterpenes from <i>Dodonaea viscosa</i>

“…Compound 1 was identified as a clerodane-type diterpene derivative by its characteristic 1 H-and 13 C-NMR (Table 1) and its heteronuclear single quantum coherence (HSQC) spectra, in which a tertiary methyl group appeared as a singlet at δ H 0.67, δ C 17.4 was assigned to CH 3 -16, a secondary methyl group was a doublet at δ H 0.95 (d, J = 6.9 Hz), and δ C 16.4 was assigned to CH 3 -13. 31) The presence of an α,β-unsaturated γ-lactone moiety was evident from the 1 H-NMR signals of δ H 6.75 (dd, J = 7.6, 2.1 Hz) for an olefinic β-proton at C-3 (δ C 138.1). In addition, the 1 H-signals at δ 4.02 (1H, d, J = 8.2-Hz) and δ 4.41 (1H, d, J = 8.2 Hz) were for oxymethylene at C-15 (δ C 73.4).…”

Dietary Diterpenoids

“…A number of the papers concerning bioconversion of terpenoids, especially mono-, sesqui-, and diterpenoids, have been reported Noma 2010, 2020;Bhatti and Khera 2014;Frij et al 2011;Monteiro et al 2017;Noma and Asakawa 2020;Rajamanikyam et al 2017;Silva et al 2013;Sultana and Saify 2012). Abietanes, cembrane, clerodanes, kauranes, labdanes, pimaranes, and taxanes and some minor skeletal diterpenoids have been carried out by enzymatical and in situ biotransformation in mammals in order to know the fetal (pathway of substrate) in our body and to obtain some functional substances for application to cosmetics, medicinal, and agricultural drugs as well as food additives and beverages.…”