Synonyms: arenaemycin E, PA 132
|Superclasses:||a lipid → an isoprenoid → a terpenoid → a sesquiterpenoid|
|a secondary metabolite → a terpenoid → a sesquiterpenoid|
|a secondary metabolite → a xenobiotic → an antibiotic|
Pentalenolactone is a widely occurring sesquiterpenoid antibiotic produced by some Streptomyces strains. It was first reported under the name PA 132 in 1957 [Koe57], and subsequently isolated from more than 30 species [Takeuchi69, Martin70]. A similar compound, called arenaemycin, was isolated from Streptomyces arenae strain Tii 469. Several forms of arenaemycin were identified -a chlorhydrine (arenaemycin C), a diol (arenaemycin D) and an epoxide (arenaemycin E) [KellerSchierlei72]. Soon after it was shown that arenaemycin E and pentalenolactone were identical [Hartmann78].
Pentalenolactone is a specific irreversible inhibitor of the glycolytic enzyme NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 22.214.171.124), (but not of the NADP-dependent enzyme, EC 126.96.36.199, which is found in plants and in some Streptomyces strains) [Hartmann78, Duszenko82, Duszenko86]. During the phase of pentalenolactone production, Streptomyces arenae expresses a pentalenolactone-insensitive isoform of GAPDH [Maurer83, Frohlich89, Frohlich96].
The compound exerts its antibiotic action against both Gram-positive and Gram-negative bacteria as well as fungi and protozoa, by a reaction of the electrophilic epoxylactone moiety with the active-site cysteine of GAPDH [Cane89, Willson94, Cane94]. Four molecules of the antibiotic bind to each homotetramer of the enzyme.
Pentalenolactone is also a potent and specific antiviral agent, inhibiting the replication of DNA viruses, such as the causal agent of herpes simplex HSV-1 and HSV-2 [Nakagawa85], and can inhibit vascular smooth muscle cell proliferation [Ikeda01].
Chemical Formula: C15H15O5
Molecular Weight: 275.28 Daltons
Monoisotopic Molecular Weight: 276.0997736241 Daltons
Standard Gibbs Free Energy of Change Formation (ΔfG'° in kcal/mol): -1.965258 [Latendresse13]
Reactions known to produce the compound:
In Transport reactions:
a xenobiotic[cytosol] + ATP + H2O ↔ a xenobiotic[extracellular space] + ADP + phosphate
Cane94: Cane DE, Sohng JK (1994). "Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone. 2. Identification of the site of alkylation by tetrahydropentalenolactone." Biochemistry 33(21);6524-30. PMID: 8204587
Frohlich89: Frohlich KU, Wiedmann M, Lottspeich F, Mecke D (1989). "Substitution of a pentalenolactone-sensitive glyceraldehyde-3-phosphate dehydrogenase by a genetically distinct resistant isoform accompanies pentalenolactone production in Streptomyces arenae." J Bacteriol 171(12);6696-702. PMID: 2592349
Frohlich96: Frohlich KU, Kannwischer R, Rudiger M, Mecke D (1996). "Pentalenolactone-insensitive glyceraldehyde-3-phosphate dehydrogenase from Streptomyces arenae is closely related to GAPDH from thermostable eubacteria and plant chloroplasts." Arch Microbiol 165(3);179-86. PMID: 8599535
Maurer83: Maurer KH, Pfeiffer F, Zehender H, Mecke D (1983). "Characterization of two glyceraldehyde-3-phosphate dehydrogenase isoenzymes from the pentalenolactone producer Streptomyces arenae." J Bacteriol 153(2);930-6. PMID: 6822480
Willson94: Willson M, Lauth N, Perie J, Callens M, Opperdoes FR (1994). "Inhibition of glyceraldehyde-3-phosphate dehydrogenase by phosphorylated epoxides and alpha-enones." Biochemistry 33(1);214-20. PMID: 8286343
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