https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Evolution of Protein Molecules

'The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle These acetylation patterns may direct histone assembly and help regulate the unfolding and activity of genes

Histone acetylation in chromatin structure and transcription

Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.

/pdf/bioprospecting-for-microbial-endophytes-and-their-natural-1urge3dlj5.pdf

Bioprospecting for Microbial Endophytes and Their Natural Products

The endophytic continuum.

A novel fungal metabolite, apicidin [cyclo(N-O-methyl-L-tryptophanyl-L -isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium berghei malaria in mice. Many Apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and new therapeutic agents are urgently needed. Apicidin's antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), which induces hyperacetylation of histones in treated parasites. The acetylation-deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells. Other known HDA inhibitors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of novel antiparasitic agents.

/pdf/apicidin-a-novel-antiprotozoal-agent-that-inhibits-parasite-5cla3iy5dh.pdf

Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase

An efficient method by which to bring tropical leaf-litter fungi into culture was sought in order to survey these organisms for pharmacologically useful metabolites. A simplified particle-filtratio...

Abundance and diversity of microfungi in leaf litter of a lowland rain forest in Costa Rica

Equisetin and a novel opposite stereochemical homolog phomasetin, two fungal metabolites as inhibitors of HIV-1 integrase

The potent insecticidal agent nodulisporic acid A (1a), representative of a new class of indole terpenes, was isolated from fermentations of a Nodulisporium sp. Nodulisporic acid A was active against the larvae of the blowfly and mosquito at sub-part-per-million levels. The structure followed mainly from a consideration of spectroscopic evidence, including Dunkel's computerized 2D INADEQUATE analysis. The relative stereochemistry of the eastern and western hemispheres of 1a and its methyl ester, 1b, were independently determined on the basis of ROESY, NOESY, NOEDS, and Jvic evidence. By employing the same methods, the complete relative stereochemistry was determined by analysis of suitable transformation products, using the reduced ‚-ketodihydropyrrole ring as a stereochemical bridge between the two zones. These results were confirmed by X-ray analysis of the 7-p-bromobenzoate methyl ester derivative, 1c. The absolute stereochemistry was established by application of the advanced Mosher method to methyl ester 1b. Of biogenetic interest is the presence of a unique isoprenylated indole moiety not previously found in other indole mycotoxins. The development of resistance to existing insecticides and the desire to have compounds with less mammalian and environmental toxicity continues to spur the search for novel insecticides. Screening culture extracts using the larvae of the mosquito, Aedes aegypti, has been well documented as a viable approach to discovering new insecticidal activities. 1a A unique macrocyclic lactone, spinosyns, now under development as a crop protection agent, was detected using the mosquito larvae assay and was isolated from Saccharopolyspora spinosa. 1c Another very useful assay involves the larvae of the blowfly, Lucilia seracata. Either of the assays can be used to measure insecticidal activities of agents such as avermectins or milbemycins. 1b,d In our ongoing screening program for biologi- cally active natural products, we have isolated a novel indole terpene designated nodulisporic acid A (1a) from a Nodulispo- rium sp. as a potent insecticide. We describe herein the isolation and structure elucidation of 1a, including the relative and absolute stereochemistry, solution conformation, and biological activity. A number of chemical transformations are also described.

Nodulisporic Acid A, a Novel and Potent Insecticide from a Nodulisporium Sp. Isolation, Structure Determination, and Chemical Transformations

The microfungal flora and community structure of the bark of Carpinus caroliniana is described as perceived by a direct isolation method. Twenty-four bark discs were removed from 10 trees at five different sites in New Jersey and West Virginia and applied to three different isolation media. From 1200 bark discs from 50 trees, 155 species of fungi were isolated. The overall recovery rate was 11.5 species/tree. A medium with cycloheximide gave the highest species recovery rates and isolated the highest percentage of all the species recovered. A medium of malt–yeast extract gave the most isolates but lowest species recovery rate. Eleven of the 12 dominant species were preferentially isolated on one of the three isolation media. The community structure of the fungi recovered from Carpinus bark exhibited the typical dominance–diversity curve that has been reported for other saprobic fungal communities. Generally, the floristic composition was similar to the bark of other tree species previously studied in temp...

Jon D. Polishook

Papers

Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase

Abundance and diversity of microfungi in leaf litter of a lowland rain forest in Costa Rica

Equisetin and a novel opposite stereochemical homolog phomasetin, two fungal metabolites as inhibitors of HIV-1 integrase

Nodulisporic Acid A, a Novel and Potent Insecticide from a Nodulisporium Sp. Isolation, Structure Determination, and Chemical Transformations

Microfungi from Carpinus caroliniana