Fellutamide

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Fellutamide A.svg
Fellutamide A
Fellutamide B.svg
Fellutamide B

Fellutamides are tripeptide derivatives from Penicillium fellutanum and other fungi. They are potent proteasome inhibitor that stimulates nerve growth factor synthesis in vitro . [1] [2]

Fellutamides A and F were first isolated from Aspergillus versicolor . [3] [4] Fellutamides C and D were first isolated from an undescribed Metulocladosporiella (Chaetothyriales). [5]

Fellutamide B strongly inhibits the growth of the tuberculosis-causing bacterium Mycobacterium tuberculosis . [6] Its biosynthetic pathway has been determined in the filamentous fungus Aspergillus nidulans . [7]

Related Research Articles

<i>Mycobacterium</i> Genus of bacteria

Mycobacterium is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy in humans. The Greek prefix myco- means 'fungus', alluding to this genus' mold-like colony surfaces. Since this genus has cell walls with a waxy lipid-rich outer layer that contains high concentrations of mycolic acid, acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.

<i>Aspergillus fumigatus</i> Species of fungus

Aspergillus fumigatus is a species of fungus in the genus Aspergillus, and is one of the most common Aspergillus species to cause disease in individuals with an immunodeficiency.

<i>Aspergillus</i> Genus of fungi

Aspergillus is a genus consisting of several hundred mould species found in various climates worldwide.

<i>Aspergillus nidulans</i> Species of fungus

Aspergillus nidulans is one of many species of filamentous fungi in the phylum Ascomycota. It has been an important research organism for studying eukaryotic cell biology for over 50 years, being used to study a wide range of subjects including recombination, DNA repair, mutation, cell cycle control, tubulin, chromatin, nucleokinesis, pathogenesis, metabolism, and experimental evolution. It is one of the few species in its genus able to form sexual spores through meiosis, allowing crossing of strains in the laboratory. A. nidulans is a homothallic fungus, meaning it is able to self-fertilize and form fruiting bodies in the absence of a mating partner. It has septate hyphae with a woolly colony texture and white mycelia. The green colour of wild-type colonies is due to pigmentation of the spores, while mutations in the pigmentation pathway can produce other spore colours.

Mycolic acids are long fatty acids found in the cell walls of Mycobacteriales taxon, a group of bacteria that includes Mycobacterium tuberculosis, the causative agent of the disease tuberculosis. They form the major component of the cell wall of many Mycobacteriales species. Despite their name, mycolic acids have no biological link to fungi; the name arises from the filamentous appearance their presence gives Mycobacteriales under high magnification. The presence of mycolic acids in the cell wall also gives Mycobacteriales a distinct gross morphological trait known as "cording". Mycolic acids were first isolated by Stodola et al. in 1938 from an extract of M. tuberculosis.

<span class="mw-page-title-main">Gliotoxin</span> Chemical compound

Gliotoxin is a sulfur-containing mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by several species of fungi, especially those of marine origin. It is the most prominent member of the epipolythiopiperazines, a large class of natural products featuring a diketopiperazine with di- or polysulfide linkage. These highly bioactive compounds have been the subject of numerous studies aimed at new therapeutics. Gliotoxin was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabolite that is one of the most abundantly produced metabolites in human invasive Aspergillosis (IA).

<span class="mw-page-title-main">Sterigmatocystin</span> Chemical compound

Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.

<span class="mw-page-title-main">Salinosporamide A</span> Chemical compound

Salinosporamide A (Marizomib) is a potent proteasome inhibitor being studied as a potential anticancer agent. It entered phase I human clinical trials for the treatment of multiple myeloma, only three years after its discovery in 2003. This marine natural product is produced by the obligate marine bacteria Salinispora tropica and Salinispora arenicola, which are found in ocean sediment. Salinosporamide A belongs to a family of compounds, known collectively as salinosporamides, which possess a densely functionalized γ-lactam-β-lactone bicyclic core.

<span class="mw-page-title-main">Isocitrate lyase</span>

Isocitrate lyase, or ICL, is an enzyme in the glyoxylate cycle that catalyzes the cleavage of isocitrate to succinate and glyoxylate. Together with malate synthase, it bypasses the two decarboxylation steps of the tricarboxylic acid cycle and is used by bacteria, fungi, and plants.

<span class="mw-page-title-main">Beta-ketoacyl-ACP synthase III</span> Enzyme

In enzymology, a β-ketoacyl-[acyl-carrier-protein] synthase III (EC 2.3.1.180) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Oxathiazolones</span> Chemical compound

The oxathiazolones are a family of heterocyclic compounds in which the parent derivative has the molecular formula C2HNO2S and for which multiple isomers are known. The two known isomers with the highest profile in the literature are 1,3,4-oxathiazol-2-one and 1,4,2-oxathiazol-5-one.

<span class="mw-page-title-main">Versicolamide B</span>

(-)-Versicolamide B and (+)-Versicolamide B are spiroindole alkaloids isolated from the fungus Aspergillus that belong to a class of naturally occurring 2,5-diketopiperazines. The versicolamides are structurally complex spiro-cyclized versions of prenylated cyclo(L-Trp-L-Pro) derivatives which possess a unique spiro-fusion to a pyrrolidine at the 3-position of the oxindole core together with the bicyclo[2.2.2]diazaoctane ring system. While (-)-versicolamide B was isolated from the marine fungus Aspergillus sp. the enantiomer (+)-versicolamide B was isolated from the terrestrial fungi Aspergillus versicolor NRRL. The total asymmetric syntheses of both enantiomers have been achieved and the implications of their biosynthesis have been investigated.

<i>Aspergillus versicolor</i> Species of fungus

Aspergillus versicolor is a slow-growing species of filamentous fungus commonly found in damp indoor environments and on food products. It has a characteristic musty odor associated with moldy homes and is a major producer of the hepatotoxic and carcinogenic mycotoxin sterigmatocystin. Like other Aspergillus species, A. versicolor is an eye, nose, and throat irritant.

<span class="mw-page-title-main">Pelanserin</span> Chemical compound

Pelanserin (TR2515) is an antagonist of the 5-HT2 and α1-adrenergic receptors.

<span class="mw-page-title-main">Dideoxyverticillin A</span> Chemical compound

Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine initially isolated from the marine fungus Penicillium sp. in 1999. It has also been found in the marine fungus Bionectriaceae, and belongs to a class of naturally occurring 2,5-diketopiperazines.

<span class="mw-page-title-main">Aspergillomarasmine A</span> Chemical compound

Aspergillomarasmine A is an polyamino acid naturally produced by the mold Aspergillus versicolor. The substance has been reported to inhibit two antibiotic resistance carbapenemase proteins in bacteria, New Delhi metallo-beta-lactamase 1 (NDM-1) and Verona integron-encoded metallo-beta-lactamase (VIM-2), and make those antibiotic-resistant bacteria susceptible to antibiotics. Aspergillomarasmine A is toxic to leaves of barley and other plants, being termed as "Toxin C" when produced by Pyrenophora teres.

Medicinal fungi are fungi that contain metabolites or can be induced to produce metabolites through biotechnology to develop prescription drugs. Compounds successfully developed into drugs or under research include antibiotics, anti-cancer drugs, cholesterol and ergosterol synthesis inhibitors, psychotropic drugs, immunosuppressants and fungicides.

Aspergillus unguis is a species of fungus in the genus Aspergillus, and the asexual state (anamorph) of Emericella unguis. Aspergillus unguis is a filamentous soil-borne fungus found on decomposing plant matter and other moist substrates including with building materials and household dust. Aspergillus unguis occurs mainly in tropical and subtropical soils but has also been isolated from various marine and aquatic habitats. The species was first isolated in 1935 by Weill and L. Gaudin. Historically, A. unguis was assigned to the A. nidulans group, a common group of soil-borne fungi due to the resemblance of its ascospores and cleistothecia to those of Emericella nidulans. Aspergillus unguis is distinctive, however, in possessing spicular hyphae. A number of synonyms have been collapsed into this species, including Sterigmatocystis unguis, Aspergillus laokiashanensis and Aspergillus mellinus.

Proteasomeaccessory factor E is an ATP-independent proteasome activator of Mycobacterium tuberculosis that forms 12-fold symmetric rings and interacts with the 20S proteasome core particle through a conserved carboxyl-terminal motif to activate peptide and protein degradation.

Gladiolin is a polyketide natural product produced by Burkholderia gladioli BCC0238 which is isolated from sputum of cystic fibrosis patients. It was found to be a novel macrolide antibiotic which presented an activity against Mycobacterium tuberculosis. Gladiolin is structurally much more stable than its analogue etnangien as an efficient myxobacterial RNA polymerase inhibitor due to the lack of highly labile hexaene moiety in gladiolin. The good activity and high stability of gladiolin offers it the potential for further development as an antibiotic against antibiotic-resistant M. tuberculosis.

References

  1. Hines J, Groll M, Fahnestock M, Crews CM (May 2008). "Proteasome inhibition by fellutamide B induces nerve growth factor synthesis". Chemistry & Biology. 15 (5): 501–12. doi:10.1016/j.chembiol.2008.03.020. PMC   2485210 . PMID   18482702.
  2. Yamaguchi K, Tsuji T, Wakuri S, Yazawa K, Kondo K, Shigemori H, Kobayashi J (February 1993). "Stimulation of nerve growth factor synthesis and secretion by fellutamide A in vitro". Bioscience, Biotechnology, and Biochemistry. 57 (2): 195–9. doi:10.1271/bbb.57.195. PMID   7763492.
  3. Lee, Yoon-Mi; Dang, Hung The; Hong, Jong-Ki; Lee, Chong-O.; Bae, Kyung-Sook; Kim, Dong-Kyoo; Jung, Jee-H. (2010). "A Cytotoxic Lipopeptide from the Sponge-Derived Fungus Aspergillus versicolor". Bulletin of the Korean Chemical Society. 31: 205–208. doi: 10.5012/bkcs.2010.31.01.205 .
  4. Lee, Yoon-Mi; Dang, Hung The; Li, Jianlin; Zhang, Ping; Hong, Jong-Ki; Lee, Chong-O.; Jung, Jee-H. (2011). "A Cytotoxic Fellutamide Analogue from the Sponge-Derived Fungus Aspergillus versicolor". Bulletin of the Korean Chemical Society. 32 (10): 3817–3820. doi: 10.5012/bkcs.2011.32.10.3817 .
  5. Xu, Deming; Ondeyka, John; Harris, Guy H.; Zink, Deborah; Kahn, Jennifer Nielsen; Wang, Hao; Bills, Gerald; Platas, Gonzalo; Wang, Wenxian; Szewczak, Alexander A.; Liberator, Paul; Roemer, Terry; Singh, Sheo B. (2011). "Isolation, Structure, and Biological Activities of Fellutamides C and D from an Undescribed Metulocladosporiella (Chaetothyriales) Using the Genome-Wide Candida albicans Fitness Test". Journal of Natural Products. 74 (8): 1721–1730. doi:10.1021/np2001573. PMID   21761939.
  6. Lin G, Li D, Chidawanyika T, Nathan C, Li H (September 2010). "Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome". Archives of Biochemistry and Biophysics. 501 (2): 214–20. doi:10.1016/j.abb.2010.06.009. PMC   2930046 . PMID   20558127.
  7. Yeh HH, Ahuja M, Chiang YM, Oakley CE, Moore S, Yoon O, Hajovsky H, Bok JW, Keller NP, Wang CC, Oakley BR (August 2016). "Resistance Gene-Guided Genome Mining: Serial Promoter Exchanges in Aspergillus nidulans Reveal the Biosynthetic Pathway for Fellutamide B, a Proteasome Inhibitor". ACS Chemical Biology. 11 (8): 2275–84. doi:10.1021/acschembio.6b00213. PMC   6457343 . PMID   27294372.