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{{chembox |
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| verifiedrevid = 400143927 |
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| verifiedrevid = 443611742 |
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| ImageFile = Lipstatin.svg |
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| ImageFile = Lipstatin.svg |
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| ImageSize = 250px |
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| ImageSize = 250px |
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| IUPACName = <br>3-methyl-pentanoate |
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| SystematicName = (2''S'',4''Z'',7''Z'')-1-trideca-4,7-dien-2-yl (2''S'')-2-formamido-4-methylpentanoate |
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| OtherNames = (2''S'',4''Z'',7''Z'')-1--4,7-tridecadien-2-yl ''N''-formyl-<small>L</small>-leucinate |
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| OtherNames = |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 7981411 |
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| ChemSpiderID = 7981411 |
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| InChI = 1/C29H49NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h12-13,15-16,22-27H,5-11,14,17-21H2,1-4H3,(H,30,31)/b13-12-,16-15-/t24-,25-,26-,27-/m0/s1 |
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| InChI = 1/C29H49NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h12-13,15-16,22-27H,5-11,14,17-21H2,1-4H3,(H,30,31)/b13-12-,16-15-/t24-,25-,26-,27-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = OQMAKWGYQLJJIA-CUOOPAIESA-N |
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| StdInChIKey = OQMAKWGYQLJJIA-CUOOPAIESA-N |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = 96829-59-3 |
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| CASNo = 96829-59-3 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| MeSHName = Lipstatin |
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| PubChem = 9805651 |
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| UNII = UBD38W8LEW |
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| MeSHName = Lipstatin |
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| ChemSpider = 7981411 |
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| PubChem = 9805651 |
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| SMILES = O=C(O(C1OC(=O)1CCCCCC)C\C=C/C\C=C/CCCCC)(NC=O)CC(C)C |
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| SMILES = O=C(O(C1OC(=O)1CCCCCC)C\C=C/C\C=C/CCCCC)(NC=O)CC(C)C |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=29 | H = 49 | N=1 | O=5 |
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| Formula = C<sub>29</sub>H<sub>49</sub>NO<sub>5</sub> |
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| Appearance = |
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| MolarMass = 491.703 g/mol |
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| Section3 = {{Chembox Hazards |
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'''Lipstatin''' is a potent, ] ] of ]. It is a ], and was first isolated from the ] '']''.<ref>{{cite journal |author=Weibel E, Hadvary P, Hochuli E, Kupfer E, Lengsfeld H |title=Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity |journal=J Antibiot (Tokyo) |volume=40 |issue=8 |pages=1081–5 |year=1987 |pmid=3680018}}</ref> |
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'''Lipstatin''' is a potent, ] ] of ]. It is a ] that was first isolated from the ] '']''.<ref>{{cite journal |vauthors=Weibel E, Hadvary P, Hochuli E, Kupfer E, Lengsfeld H |title=Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity |journal=J Antibiot (Tokyo) |volume=40 |issue=8 |pages=1081–5 |year=1987 |pmid=3680018 |doi=10.7164/antibiotics.40.1081|doi-access=free }}</ref> |
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The popular ] drug ] (trade names '''Xenical''' and '''alli''') is a ] derivative of lipstatin. |
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The popular ] drug ] (trade names '''Xenical''' and '''alli''') is a ] derivative of lipstatin. |
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==References== |
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== Biosynthesis == |
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] |
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Lipstatin is composed of a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-β-lactone 22 carbon backbone from ] pathway and an ''N''-formyl-] group ester linked to the 5-hydroxyl group of the back bone. The composts of the lipstatin are ultimately from ], ], and ].<ref name=":0">{{Cite journal|last1=Bai|first1=Tingli|last2=Zhang|first2=Daozhong|last3=Lin|first3=Shuangjun|last4=Long|first4=Qingshan|last5=Wang|first5=Yemin|last6=Ou|first6=Hongyu|last7=Kang|first7=Qianjin|last8=Deng|first8=Zixin|last9=Liu|first9=Wen|date=2014-12-15|title=Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase|journal=Applied and Environmental Microbiology|language=en|volume=80|issue=24|pages=7473–7483|doi=10.1128/AEM.01765-14|issn=0099-2240|pmc=4249243|pmid=25239907|bibcode=2014ApEnM..80.7473B }}</ref> |
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The 22 carbon β-lactone moiety is derived from ] between 3-hydroxytetradeca-5,8-dienyl-CoA derived from ] and hexyl-malonyl-ACP derived from ].<ref name=":0" /> <ref>{{Cite journal|last1=Goese|first1=Markus|last2=Eisenreich|first2=Wolfgang|last3=Kupfer|first3=Ernst|last4=Stohler|first4=Peter|last5=Weber|first5=Wolfgang|last6=Leuenberger|first6=Hans G.|last7=Bacher|first7=Adelbert|date=2001-06-01|title=Biosynthesis of Lipstatin. Incorporation of Multiply Deuterium-Labeled (5Z,8Z)-Tetradeca-5,8-dienoic Acid and Octanoic Acid|journal=The Journal of Organic Chemistry|volume=66|issue=13|pages=4673–4678|doi=10.1021/jo010230b|pmid=11421791 |issn=0022-3263}}</ref><ref name=":1" />Linoleic acid is first attached to ] through some ] homologue synthesized by lipstatin biosynthetic operons (''Lst'') and goes through two ] to hydroxytetradeca-5,8-dienyl-CoA. 3’ hydroxyl group from solution H<sub>2</sub>O is added by ] homologue followed by ] homologue.<ref>{{Cite journal|last1=Goese|first1=Markus|last2=Eisenreich|first2=Wolfgang|last3=Kupfer|first3=Ernst|last4=Weber|first4=Wolfgang|last5=Bacher|first5=Adelbert|date=2000-07-14|title=Biosynthetic Origin of Hydrogen Atoms in the Lipase Inhibitor Lipstatin|journal=Journal of Biological Chemistry|language=en|volume=275|issue=28|pages=21192–21196|doi=10.1074/jbc.M003094200|issn=0021-9258|pmid=10801870|doi-access=free}}</ref> Octanoic acid is also attached to ] through similar ] homologue (''LstC'') to form ]. Octanoyl-CoA is 2’ carboxylated and loaded to ] (ACP) borrowed from primary metabolism to form hexyl-malonyl-ACP.<ref name=":1">{{Cite journal|last1=Demirev|first1=Atanas V.|last2=Khanal|first2=Anamika|last3=Sedai|first3=Bhishma R.|last4=Lim|first4=Si Kyu|last5=Na|first5=Min Kyun|last6=Nam|first6=Doo Hyun|date=2010-05-02|title=The role of acyl-coenzyme A carboxylase complex in lipstatin biosynthesis of Streptomyces toxytricini|journal=Applied Microbiology and Biotechnology|language=en|volume=87|issue=3|pages=1129–1139|doi=10.1007/s00253-010-2587-2|issn=0175-7598|pmc=2886142|pmid=20437235}}</ref> |
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The ] ring is formed by reduction of 3-] by 3-hydroxysteroid ] homologue followed by a spontaneously ] of the 3-] on the carbonyl of the ACP-tether acyl intermediate. This step follows the ] of the ''N''-formyl-L-leucine group.<ref name=":0" /> |
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The ''N''-formyl-L-leucine group is derived from ]. L-leucine was activated by ''LstE'' forming ] and its ] is ] by ''LstF''. Finally, 5-hydroxyl of 22 carbon β-lactone backbone ] on the acyl carbon of the formyl-leucine and forms the lipstatin.<ref name=":0" /> |
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==See also== |
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* ] |
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== References == |
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