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MetaCyc Compound: pentalenolactone

Synonyms: arenaemycin E, PA 132

Superclasses: a lipidan isoprenoida terpenoida sesquiterpenoid
a secondary metabolitea terpenoida sesquiterpenoid
a secondary metabolitea xenobiotican 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, (but not of the NADP-dependent enzyme, EC, 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

pentalenolactone compound structure

SMILES: CC3(C(C)C4(C=C(C([O-])=O)[CH]2(C(C1(OC1)C(=O)OC2)(C=3)4)))

InChI: InChI=1S/C15H16O5/c1-7-4-14-10(8(7)2)3-9(12(16)17)11(14)5-19-13(18)15(14)6-20-15/h3-4,8,10-11H,5-6H2,1-2H3,(H,16,17)/p-1/t8-,10?,11+,14?,15?/m1/s1


Unification Links: ChEBI:70790, PubChem:90658936

Standard Gibbs Free Energy of Formation (ΔfG in kcal/mol): -1.965258Inferred by computational analysis [Latendresse13]

Reactions known to produce the compound:

pentalenolactone biosynthesis :
pentalenolactone F + 2 a reduced ferredoxin [iron-sulfur] cluster + oxygen + 2 H+pentalenolactone + 2 an oxidized ferredoxin [iron-sulfur] cluster + 2 H2O

In Transport reactions:
a xenobiotic[cytosol] + ATP + H2O ↔ a xenobiotic[extracellular space] + ADP + phosphate

Created 26-Sep-2011 by Caspi R, SRI International


Cane89: Cane DE, Sohng JK (1989). "Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone: kinetic and mechanistic studies." Arch Biochem Biophys 270(1);50-61. PMID: 2930199

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

Duszenko82: Duszenko M, Balla H, Mecke D (1982). "Specific inactivation of glucose metabolism from eucaryotic cells by pentalenolactone." Biochim Biophys Acta 714(2);344-50. PMID: 7034785

Duszenko86: Duszenko M, Mecke D (1986). "Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone in Trypanosoma brucei." Mol Biochem Parasitol 19(3);223-9. PMID: 3736593

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

Hartmann78: Hartmann S, Neeff J, Heer U, Mecke D (1978). "Arenaemycin (pentalenolactone): a specific inhibitor of glycolysis." FEBS Lett 93(2);339-42. PMID: 361434

Ikeda01: Ikeda M, Fukuda A, Takagi M, Morita M, Shimada Y (2001). "Inhibitory effect of pentalenolactone on vascular smooth muscle cell proliferation." Eur J Pharmacol 411(1-2);45-53. PMID: 11137857

KellerSchierlei72: Keller-Schierlein, W., Lemke, J., Nyfeler, R., Z&her, H. (1972). "Stoffwechselprodukte von Mikroorganismen." Archiv für Mikrobiologie 84:301-316.

Koe57: Koe BK, Sobin BA, Celmer WD (1957). "PA 132, a new antibiotic. I. Isolation and chemical properties." Antibiot Annu 1956-1957:672-5. PMID: 13425447

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Martin70: Martin DG, Slomp G, Mizsak S, Duchamp DJ, Chidester CG (1970). "The structure and absolute configuration of pentalenolactone (PA 132)." Tetrahedron Lett (56);4901-4. PMID: 5500064

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

Nakagawa85: Nakagawa A, Tomoda H, Hao MV, Okano K, Iwai Y, Omura S (1985). "Antiviral activities of pentalenolactones." J Antibiot (Tokyo) 38(8);1114-5. PMID: 4044412

Takeuchi69: Takeuchi S, Ogawa Y, Yonehara H (1969). "The structure of pentalenolactone (PA-132)." Tetrahedron Lett (32);2737-40. PMID: 5808206

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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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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