Occurrence and Properties of Thiosilvatins

Abstract

The spread of studies on biodiversity in different environmental contexts is particularly fruitful for natural product discovery, with the finding of novel secondary metabolites and structural models, which are sometimes specific to certain organisms. Within the large class of the epipolythiodioxopiperazines, which are typical of fungi, thiosilvatins represent a homogeneous family that, so far, has been reported in low frequency in both marine and terrestrial contexts. However, recent observations indicate that these compounds have been possibly neglected in the metabolomic characterization of fungi, particularly from marine sources. Aspects concerning occurrence, bioactivities, structural, and biosynthetic properties of thiosilvatins are reviewed in this paper.

Secondary Metabolites of Lasiodiplodia theobromae: Distribution, Chemical Diversity, Bioactivity, and Implications of Their Occurrence

“…In fact, the increasing number of studies on fungal genome sequences showed that the capability of fungi to produce secondary metabolites has been largely underestimated, because many of the fungal secondary metabolite biosynthetic gene clusters are silent under standard cultivation conditions. A large number of genes discovered by bioinformatic analyses based on polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, putatively involved in secondary metabolites biosynthesis, are much higher than estimated, even in fungal species extensively studied for the production of secondary metabolites [ 125 , 126 ].…”

Identification of the Main Metabolites of a Marine-Derived Strain of Penicillium brevicompactum Using LC and GC MS Techniques

“…The second purified product, cis-bis(methylthio)silvatin, is a member of thiosilvatins, a homogeneous family of compounds within the epipolythiodioxopiperazines, which, so far, have been reported from just 22 strains belonging to 17 fungal species from both marine and terrestrial sources. Half of these strains belong to Penicillium species, indicating that the genetic basis for thiosilvatin biosynthesis may be rooted in this genus [12]. Despite P. brevicompactum being very frequently recovered from many ecological contexts, this product has already been reported from just a single non-marine strain of this species, together with deprenyl-bis(methylthio)silvatin [18], indicative of either its infrequent occurrence or inherent difficulties in extraction and/or identification.…”

“…Our metabolomic analysis, carried out by combining several instrumental techniques and structural elucidation approaches, disclosed the ability by strain AN4 of P. brevicompactum to produce several compounds belonging to the thiosilvatin series [12], in evident connection with their biosynthetic relationships. Seven compounds in this series, of which five were not previously reported in P. brevicompactum, were detected as secondary metabolites of strain AN4.…”

“…The data in Table 1, and the corresponding EI mass spectra, were employed to assign a structure to each of the unidentified target metabolites. Hence, LC-ESI-HRMS and GC-EI-MS allowed the putative identification of other compounds (Figure 1), a number of which were found to belong to the thiosilvatin series [12]. Table 1.…”

“…The data in Table 1, and the corresponding EI mass spectra, were employed to assign a structure to each of the unidentified target metabolites. Hence, LC-ESI-HRMS and GC-EI-MS allowed the putative identification of other compounds (Figure 1), a number of which were found to belong to the thiosilvatin series [12]. It is to be specified that, unlike cis-bis(methylthio)silvatin (1), whose configuration was assigned by NMR, the determination of stereochemistry was not possible for compounds identified via MS.…”