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

Marine natural products.

Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.

https://depositonce.tu-berlin.de/bitstream/11303/5674/1/c2np20085f.pdf

Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature

Histone deacetylase (HDAC) inhibitors have been shown to be potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells in vitro and in vivo. One class of HDAC inhibitors, hydroxamic acid-based hybrid polar compounds (HPCs), induce differentiation at micromolar or lower concentrations. Studies (x-ray crystallographic) showed that the catalytic site of HDAC has a tubular structure with a zinc atom at its base and that these HDAC inhibitors, such as suberoylanilide hydroxamic acid and trichostatin A, fit into this structure with the hydroxamic moiety of the inhibitor binding to the zinc. HDAC inhibitors cause acetylated histones to accumulate in both tumor and normal tissues, and this accumulation can be used as a marker of the biologic activity of the HDAC inhibitors. Hydroxamic acid-based HPCs act selectively to inhibit tumor cell growth at levels that have little or no toxicity for normal cells. These compounds also act selectively on gene expression, altering the expression of only about 2% of the genes expressed in cultured tumor cells. In general, chromatin fractions enriched in actively transcribed genes are also enriched in highly acetylated core histones, whereas silent genes are associated with nucleosomes with a low level of acetylation. However, HDACs can also acetylate proteins other than histones in nucleosomes. The role that these other targets play in the induction of cell growth arrest, differentiation, and/or apoptotic cell death has not been determined. Our working hypothesis is that inhibition of HDAC activity leads to the modulation of expression of a specific set of genes that, in turn, result in growth arrest, differentiation, and/or apoptotic cell death. The hydroxamic acid-based HPCs are potentially effective agents for cancer therapy and, possibly, cancer chemoprevention.

/pdf/histone-deacetylase-inhibitors-inducers-of-differentiation-g9kmjv7wbj.pdf

Histone Deacetylase Inhibitors: Inducers of Differentiation or Apoptosis of Transformed Cells

3.3.1. Potential of the “Metagenome” 3016 3.3.2. Cryptic Clusters in Bacteria and Fungi 3016 3.3.3. Cyanophytes 3017 3.3.4. Marine Microbes (Non-Cyanophytes) 3018 3.3.5. Extremophiles 3018 3.3.6. Microbial Symbionts 3019 3.3.7. Plant Endophytes 3020 3.3.8. Combinatorial Biosynthesis 3020 4. Development of Drugs from Natural Products 3020 4.1. Synthesis Based on Natural Products 3021 4.1.1. Derivatization and Semisynthesis 3021 4.1.2. Total Synthesis 3021 4.1.3. Diverted Total Synthesis 3021 4.2. Natural Product-Inspired Combinatorial Synthesis 3022

Impact of natural products on developing new anti-cancer agents

A new antibiotic, trichostatin, was isolated from the metabolites of strains of Streptomyces hygroscopicus. It is active against trichophytons and some fungi. The structure was determined to be a derivative of a primary hydroxamic acid by chemical and spectroscopic evidences.

https://www.jstage.jst.go.jp/article/antibiotics1968/29/1/29_1_1/_pdf

A new antifungal antibiotic, trichostatin

from the fermentation broth of Aspergillus candidus RF-5672 (FERM BP-5882), which was isolated from a soil sample collected on Shodo Island, Kagawa Prefecture, Japan. In this communication, we report the fermentation, isolation, structure elucidation and biological properties of these terprenins. The activities of the terprenins found were evaluated with respect to proliferation of mouse spleen lymphocytes which had been stimulated with concanavalin A (Con

Terprenins, Novel Immunosuppressants Produced by Aspergillus candidus

Thiocillins I and It were isolated from the culture broth of Bacillus cereus G-15, and thiocillins II and III from that of Bacillus badius AR-91. Also, the former two were probably produced by Bacillus megatherium I-13. These antibiotics active against Gram-positive bacteria are soluble in a mixture of chloroform and methanol, show characteristic ultraviolet absorptions (maxima at ca. 275 nm and ca. 348 nm), and contain a high content of sulfur, as much as approximately 15%. They are related to each other and also to micrococcin P, but differentiated by chromatographic behaviours.

Isolation of three new antibiotics, thiocillins I, II and III, related to micrococcin P. Studies on antibiotics from the genus Bacillus. VIII.

Studies on antibiotics from the genus Bacillus. VIII. Isolation of three new antibiotics, thiocillins I, II and III, related to micrococcin P.:STUDIES ON ANTIBIOTICS FROM THE GENUS BACILLUS . VIII

A selective medium containing 25 to 50 micrograms per ml of tunicamycin was devised to isolate micromonosporae from soil samples, making possible simple, preferential isolation of a variety of Micromonospora. When a large amount of Gram-negative bacteria was present in a sample, alkaline treatment (0.01 N NaOH, 5 approximately 10 minutes at 15 degrees C) wa employed to reduce the numbers. Using the tunicamycin agar medium, 1,585 strains of presumably different micromonosporae were obtained from 400 soil samples collected from various regions around the world. In average, 4 different Micromonospora strains could be located from one soil sample. This tunicamycin method made possible a concentrated screening method for new antibiotics from Micromonospora.

Kenzo Koizumi

Papers

A new antifungal antibiotic, trichostatin

Terprenins, Novel Immunosuppressants Produced by Aspergillus candidus

Isolation of three new antibiotics, thiocillins I, II and III, related to micrococcin P. Studies on antibiotics from the genus Bacillus. VIII.

Studies on antibiotics from the genus Bacillus. VIII. Isolation of three new antibiotics, thiocillins I, II and III, related to micrococcin P.:STUDIES ON ANTIBIOTICS FROM THE GENUS BACILLUS . VIII

A selective isolation procedure for Micromonospora.