Covering: 2006 to mid-2010 Marine-derived fungi continue to produce structurally unique secondary metabolites, a considerable number of which display promising biological and pharmacological ...properties. This review gives an overview of new natural products from marine-derived fungi and their biological activities, focusing on the period from 2006 until mid-2010. Overall, 690 structures and 478 references are presented.
Terpenes from marine-derived fungi show a pronounced degree of structural diversity, and due to their interesting biological and pharmacological properties many of them have aroused interest from ...synthetic chemists and the pharmaceutical industry alike. The aim of this paper is to give an overview of the structural diversity of terpenes from marine-derived fungi, highlighting individual examples of chemical structures and placing them in a context of other terpenes of fungal origin. Wherever possible, information regarding the biological activity is presented.
The frequent re-isolation of known compounds is one of the major challenges in drug discovery. Many biosynthetic genes are not expressed under standard culture conditions, thus limiting the chemical ...diversity of microbial compounds that can be obtained through fermentation. On the other hand, the competition during co-cultivation of two or more different microorganisms in most cases leads to an enhanced production of constitutively present compounds or an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain under different fermentation conditions. Herein, we report the dual induction of newly detected bacterial and fungal metabolites by the co-cultivation of the marine-derived fungal isolate
MR2012 and two hyper-arid desert bacterial isolates
strain C34 and strain C58. Co-cultivation of the fungal isolate MR2012 with the bacterial strain C34 led to the production of luteoride D, a new luteoride derivative and pseurotin G, a new pseurotin derivative in addition to the production of terezine D and 11-
-methylpseurotin A which were not traced before from this fungal strain under different fermentation conditions. In addition to the previously detected metabolites in strain C34, the lasso peptide chaxapeptin was isolated under co-culture conditions. The gene cluster for the latter compound had been identified through genome scanning, but it had never been detected before in the axenic culture of strain C34. Furthermore, when the fungus MR2012 was co-cultivated with the bacterial strain C58, the main producer of chaxapeptin, the titre of this metabolite was doubled, while additionally the bacterial metabolite pentalenic acid was detected and isolated for the first time from this strain, whereas the major fungal metabolites that were produced under axenic culture were suppressed. Finally, fermentation of the MR2012 by itself led to the isolation of the new diketopiperazine metabolite named brevianamide X.
Nature offers a huge and only partially explored variety of small molecules with potential pharmaceutical applications. Commonly used characterization methods for natural products include ...spectroscopic techniques such as nuclear magnetic resonance spectroscopy and mass spectrometry. In some cases, however, these techniques do not succeed in the unambiguous determination of the chemical structure of unknown compounds. To validate the usefulness of scanning probe microscopy as an adjunct to the other tools available for organic structure analysis, we used the natural product cephalandole A, which had previously been misassigned, and later corrected. Our results, corroborated by density functional theory, demonstrate that direct imaging of an organic compound with atomic-resolution force microscopy facilitates the accurate determination of its chemical structure. We anticipate that our method may be developed further towards molecular imaging with chemical sensitivity, and will become generally useful in solving certain classes of natural product structures.
Macrocystis pyrifera and Lessonia spicata are economically and ecologically relevant brown seaweeds that recently have been classified as members of two separated families within Laminariales ...(kelps). Here we describe for the first time the Macrocystis pyrifera x Lessonia spicata hybridization in the wild (Chiloe Island, Southeastern Pacific), where populations of the two parents exist sympatrically. Externally, this hybrid exhibited typical features of its parents M. pyrifera (cylindrical and flexible distal stipes, serrate frond margins and presence of sporophylls) and L. spicata (rigid and flat main stipe and first bifurcation), as well as intermediate features between them (thick unfused haptera in the holdfast). Histological sections revealed the prevalence of mucilage ducts within stipes and fronds (absent in Lessonia) and fully developed unilocular sporangia in the sporophylls. Molecular analyses confirmed the presence of the two parental genotypes for ITS1 nrDNA and the M. pyrifera genotype for two predominantly maternally inherited cytoplasmic markers (COI and rbcLS spacer) in the tissue of the hybrid. A metabolome-wide approach revealed that this hybrid is more chemically reminiscent to M. pyrifera. Nevertheless, several hits were identified as Lessonia exclusive or more remarkably, not present in any of the parent. Meiospores developed into apparently fertile gametophytes, which gave rise to F1 sporophytes that reached several millimeters before suddenly dying. In-vitro reciprocal crossing of Mar Brava gametophytes from both species revealed that although it is rare, interfamilial hybridization between the two species is possible but mostly overcome by pseudogamy of female gametophytes.
Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the
genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents ...and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures
closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures
,
,
and
show a predicted high binding potential to suppress viral replication.
Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to ...the isolation of a novel Ghanaian soil bacterium,
. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A
. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of
was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of
using Group B
(GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative
biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.
Approaches for the unambiguous identification of lipophilic arsenic species in Saccharina latissima (sugar kelp) have been studied. Parallel use of high resolution ICPMS and electrospray ionization ...(ESI)-MS after separation revealed that Saccharina latissima contained three distinct classes of lipophilic As-species, a family of arsenic containing phospholipids (AsPL), all including As in the form of As–sugar–PO4, As-containing hydrocarbons (AsHC), and As-containing polyunsaturated fatty acids (AsFA). For detailed identification, the use of phospholipases, in particular phospholipase A2, was essential to define the fatty acid composition (determination of regioisomers) of the lipids without purification of the sample, while fragmentation of the molecules by MS2 measurements alone did not supply this information. Some of the identified AsPL contained unsaturated fatty acids (C16:1, C18:1 to C18:3), but saturated fatty acids dominated the AsPL. The fatty acid bound to the position 2″ was predominantly C16:0. Complete lipid hydrolysis showed that this alga did not contain arsenic containing fatty acids (AsFA) bound to complex lipids. Our investigations indicate that in addition to RP-HPLC-ICPMS/ESI-MS a range of different derivatization methods should be used for the comprehensive identification of unknown lipid-soluble arsenic compounds.
Whole-genome sequence data of the genus
have shown a far greater chemical diversity of metabolites than what have been discovered under typical laboratory fermentation conditions. In our previous ...natural product discovery efforts on
sp. MA37, a bacterium isolated from the rhizosphere soil sample in Legon, Ghana, we discovered a handful of specialised metabolites from this talented strain. However, analysis of the draft genome of MA37 suggested that most of the encoded biosynthetic gene clusters (BGCs) remained cryptic or silent, and only a small fraction of BGCs for the production of specialised metabolites were expressed when cultured in our laboratory conditions. In order to induce the expression of the seemingly silent BGCs, we have carried out a co-culture experiment by growing the MA37 strain with the Gram-negative bacterium
sp. in a co-culture chamber that allows co-fermentation of two microorganisms with no direct contact but allows exchange of nutrients, metabolites, and other chemical cues. This co-culture approach led to the upregulation of several metabolites that were not previously observed in the monocultures of each strain. Moreover, the co-culture induced the expression of the cryptic indole alkaloid BGC in MA37 and led to the characterization of the known indolocarbazole alkaloid, BE-13793C
. Neither bacterium produced compound
when cultured alone. The structure of
was elucidated by Nuclear Magnetic Resonance (NMR), mass spectrometry analyses and comparison of experimental with literature data. A putative biosynthetic pathway of
was proposed. Furthermore, BE-13793C
showed strong anti-proliferative activity against HT-29 (ATCC HTB-38) cells but no toxic effect to normal lung (ATCC CCL-171) cells. To the best of our knowledge, this is the first report for the activity of
against HT-29. No significant antimicrobial and anti-trypanosomal activities for
were observed. This research provides a solid foundation for the fact that a co-culture approach paves the way for increasing the chemical diversity of strain MA37. Further characterization of other upregulated metabolites in this strain is currently ongoing in our laboratory.
Cowpox is caused by a DNA virus known as the cowpox virus (CPXV) belonging to the
genus in the family Poxviridae. Cowpox is a zoonotic disease with the broadest host range among the known poxviruses. ...The natural reservoir hosts of CPXV are wild rodents. Recently, the cases of orthopoxviral infections have been increasing worldwide, and cowpox is considered the most common orthopoxviral infection in Europe. Cowpox is often a self-limiting disease, although cidofovir or anti-vaccinia gammaglobulin can be used in severe and disseminated cases of human cowpox. In this computational study, a molecular docking analysis of thymine- and arabinofuranosyl-thymine-related structures (
) on two cowpox-encoded proteins was performed with respect to the cidofovir standard and a 3D ligand-based pharmacophore model was generated. Three chemical structures (PubChem IDs: 123370001, 154137224, and 90413364) were identified as potential candidates for anti-cowpox agents. Further studies combining in vitro and in silico molecular dynamics simulations to test the stability of these promising compounds could effectively improve the future design of cowpox virus inhibitors, as molecular docking studies are not sufficient to consider a ligand a potential drug.
PDF
