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Revision as of 12:42, 16 September 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{chembox}} (no changed fields - added verified revid - updated 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEBI_Ref') per Chem/Drugbox validation (report [[Wikiped← Previous edit Latest revision as of 00:03, 8 December 2023 edit undo137.82.193.150 (talk) →See also 
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{{Chembox {{Chembox
| Verifiedfields = changed
⚫ | verifiedrevid = 450796655
| Watchedfields = changed
⚫ | verifiedrevid = 450797983
| ImageFile =Pikromycin.svg | ImageFile =Pikromycin.svg
| ImageSize = | ImageSize =
| IUPACName = (3R,5R,6S,7S,9R,11E,13S,14R)-14-ethyl-13-hydroxy-3,5,7,9,13-pentamethyl-2,4,10-trioxooxacyclotetradec-11-en-6-yl 3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranoside | IUPACName = (3''R'',5''R'',6''S'',7''S'',9''R'',11''E'',13''S'',14''R'')-14-Ethyl-13-hydroxy-3,5,7,9,13-pentamethyl-6--1-oxacyclotetradec-11-ene-2,4,10-trione
| SystematicName = (3''R'',5''R'',6''S'',7''S'',9''R'',11''E'',13''S'',14''R'')-6-{oxy}-14-ethyl-13-hydroxy-3,5,7,9,13-pentamethyl-1-oxacyclotetradec-11-ene-2,4,10-trione
| OtherNames = | OtherNames = Picromycin
| Section1 = {{Chembox Identifiers |Section1={{Chembox Identifiers
⚫ | CASNo = 19721-56-3
| CASNo_Ref = {{cascite|correct|??}}
⚫ | PubChem = 5282037
⚫ | CASNo = 19721-56-3
⚫ | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = FBM8G3Z439
⚫ | PubChem = 5282037
⚫ | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4445267 | ChemSpiderID = 4445267
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 29665
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C28H47NO8/c1-10-22-28(7,34)12-11-21(30)15(2)13-16(3)25(18(5)23(31)19(6)26(33)36-22)37-27-24(32)20(29(8)9)14-17(4)35-27/h11-12,15-20,22,24-25,27,32,34H,10,13-14H2,1-9H3/b12-11+/t15-,16+,17-,18+,19-,20+,22-,24-,25+,27+,28+/m1/s1 | StdInChI = 1S/C28H47NO8/c1-10-22-28(7,34)12-11-21(30)15(2)13-16(3)25(18(5)23(31)19(6)26(33)36-22)37-27-24(32)20(29(8)9)14-17(4)35-27/h11-12,15-20,22,24-25,27,32,34H,10,13-14H2,1-9H3/b12-11+/t15-,16+,17-,18+,19-,20+,22-,24-,25+,27+,28+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UZQBOFAUUTZOQE-VSLWXVDYSA-N | StdInChIKey = UZQBOFAUUTZOQE-VSLWXVDYSA-N
| SMILES = O=C2((O1O(C(N(C)C)1O)C)(C)C(C(=O)/C=C/(O)(C)(OC(=O)2C)CC)C)C | SMILES = O=C2((O1O(C(N(C)C)1O)C)(C)C(C(=O)/C=C/(O)(C)(OC(=O)2C)CC)C)C
| InChI = InChI=1S/C28H47NO8/c1-10-22-28(7,34)12-11-21(30)15(2)13-16(3)25(18(5)23(31)19(6)26(33)36-22)37-27-24(32)20(29(8)9)14-17(4)35-27/h11-12,15-20,22,24-25,27,32,34H,10,13-14H2,1-9H3/b12-11+/t15-,16+,17-,18+,19-,20+,22-,24-,25+,27+,28+/m1/s1 | InChI = InChI=1S/C28H47NO8/c1-10-22-28(7,34)12-11-21(30)15(2)13-16(3)25(18(5)23(31)19(6)26(33)36-22)37-27-24(32)20(29(8)9)14-17(4)35-27/h11-12,15-20,22,24-25,27,32,34H,10,13-14H2,1-9H3/b12-11+/t15-,16+,17-,18+,19-,20+,22-,24-,25+,27+,28+/m1/s1
}} }}
| Section2 = {{Chembox Properties |Section2={{Chembox Properties
| C=28 | H=47 | N=1 | O=8
| Formula = C<sub>28</sub>H<sub>47</sub>NO<sub>8</sub>
| MolarMass = 525.675 | Appearance =
| Appearance = | Density =
| Density = | MeltingPt =
| MeltingPt = | BoilingPt =
| BoilingPt = | Solubility =
| Solubility =
}} }}
| Section3 = {{Chembox Hazards |Section3={{Chembox Hazards
| MainHazards = | MainHazards =
| FlashPt = | FlashPt =
| Autoignition = | AutoignitionPt =
}} }}
}} }}

'''Pikromycin''' was studied by Brokmann and Hekel in 1951 and is the first antibiotic macrolide to be isolated.<ref>{{cite journal '''Pikromycin''' was studied by Brokmann and Hekel in 1951 and was the first antibiotic ] to be isolated.<ref>{{cite journal
| author = Brockmann, H. and Henkel, W. |author1=Brockmann, H. |author2=Henkel, W.
⚫ | date = 1951
|name-list-style=amp | year = 1951
| pages = 184-288 | pages = 184–288
| volume = 84 | title = Pikromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten | volume = 84 | title = Pikromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten
| journal = ntibiotica aus Actinomyceten, | journal = Ntibiotica aus Actinomyceten
| doi = 10.1002/cber.19510840306 | doi = 10.1002/cber.19510840306
}}</ref> }}</ref>
Pikromycin is synthesized through a type I ] system in ], a species of ] bacterium in the Streptomyces genus. <ref>{{cite journal Pikromycin is synthesized through a type I ] system in '']'', a species of ] bacterium in the genus '']''.<ref name="auto">{{cite journal
| author = Y. Xue and D. Sherman |author1=Y. Xue |author2=D. Sherman
| date = 2001 |name-list-style=amp | year = 2001
| pages = 15-26 | pages = 15–26
| volume = 3 | title = Biosynthesis and Combinatorial Biosynthesis of Pikromycin-Related Macrolides in Streptomyces venezuelae | volume = 3 | title = Biosynthesis and Combinatorial Biosynthesis of Pikromycin-Related Macrolides in Streptomyces venezuelae
| journal = Metabolic Engineering | journal = Metabolic Engineering
|issue=1
| doi = 10.1006/mben.2000.0167 | doi = 10.1006/mben.2000.0167
⚫ }}</ref>
|pmid=11162229
⚫ Pikromycin is derived from narbonolide, a 14-membered ring macrolide.
⚫ }}</ref>
⚫ Pikromycin is derived from ], a 14-membered ring macrolide.
<ref>{{cite journal <ref>{{cite journal
| author = Maezawa, T. Hori, A. Kinumaki and M. Suzuki | author = Maezawa, T. Hori, A. Kinumaki and M. Suzuki
| date = 1973 | year = 1973
| pages = 771-775 | pages = 771–775
| volume = 26 | title = Biological conversion of narbonolide to picromycin | volume = 26 | title = Biological conversion of narbonolide to picromycin
| journal = Metabolic Engineering | journal = The Journal of Antibiotics
| issue = 12
| doi = 10.1006/mben.2000.0167 | doi = 10.7164/antibiotics.26.771
⚫ | pmid = 4792390
| doi-access= free
}}</ref> }}</ref>
Along with the narbonolide backbone, pikromycin includes a desosamine sugar and a hydroxyl group. Although Pikromycin is not a clinically useful antibiotic, it can be used as a raw material to synthesize antibiotic ketolide compounds such as ertythromycins and new epothilones. Along with the narbonolide backbone, pikromycin includes a desosamine sugar and a hydroxyl group. Although Pikromycin is not a clinically useful antibiotic, it can be used as a raw material to synthesize antibiotic ketolide compounds such as ] and new ]s.
<ref>{{cite journal <ref>{{cite journal
| author = J.D. Kittendorf and D.H. Sherman |author1=J.D. Kittendorf |author2=D.H. Sherman
| date = 2009 |name-list-style=amp | year = 2009
| pages = 2137-2146 | pages = 2137–2146
| volume = 17 | title = The Methymycin/Pikromycin Biosynthetic Pathway: A Model for Metabolic Diversity in Natural Product | volume = 17 | title = The Methymycin/Pikromycin Biosynthetic Pathway: A Model for Metabolic Diversity in Natural Product
| journal = Bioorg Med Chem | journal = Bioorg Med Chem
|issue=6
| doi = 10.1016/j.bmc.2008.10.082 | doi = 10.1016/j.bmc.2008.10.082
}}</ref>
|pmc=2843759 | pmid=19027305}}</ref>

__TOC__
==Biosynthesis == ==Biosynthesis ==


The pikromycin polyketide synthase of Streptomyces venezuelae contains four polypeptides: PikAI, PikAII, PikAIII, and PikAIV. These polypeptides contain a loading module, six extension molecules, and a thioesterase domain that that terminated the biosynthetic procedure. The pikromycin polyketide synthase of ''Streptomyces venezuelae'' contains four polypeptides: PikAI, PikAII, PikAIII, and PikAIV. These polypeptides contain a loading module, six extension molecules, and a ] domain that terminated the biosynthetic procedure.
<ref>{{cite journal <ref>{{cite journal
| author = S. Guptaa, V. Lakshmanan, B.S. Kima, R. Fecik, and K. A. Reynolds |author1=S. Guptaa |author2=V. Lakshmanan |author3=B.S. Kima |author4=R. Fecik |author5=K. A. Reynolds |name-list-style=amp | year = 2008
| date = 2008 | pages = 1609–1616
⚫ | volume = 9 | title = Generation of Novel Pikromycin Antibiotic Products Through Mutasynthesis
⚫ | pages = 1609-1616
⚫ | journal = ChemBioChem
⚫ | volume = 10 | title = Generation of Novel Pikromycin Antibiotic Products Through Mutasynthesis
⚫ |issue=10 | doi = 10.1002/cbic.200700635
⚫ | journal = Chembiochem
|pmc=2614871 | pmid=18512859}}</ref>
⚫ | doi = 10.1002/cbic.200700635
Recently electron cryo-microscopy have been used to determine sub-nanometre-resolution three- dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture.
}}</ref>
⚫ <ref>{{cite journal
⚫ In Figure 1, each circle corresponds to a PKS mutilifuctional protein, where ACP is acyl carrier protein, KS is keto-ACP synthase, KSQ is a keto-ACP synthase like domain, AT is acyltransferase, KR is keto ACP reductase, KR with cross is inactive KR, DH is hydroxyl-thioester dehydratase, ER is enoyl reductase, TEI is thioesterase domain I, TEII is type II thioesterase.
|author1=S. Dutta |author2=J. R. Whicher |author3=D. A. Hansen |author4=W. A. Hale |author5=J. A. Chemler |author6=G. R. Congdon |author7=A. R. H. Narayan |author8=K. Håkansson |author9=D. H. Sherman |author10=J. L. Smith |author11=G. Skiniotis | year = 2014
⚫ | pages = 512–517
| volume = 510 | title = Structure of amodular polyketide synthase
⚫ | journal = Nature
|issue=7506 | doi = 10.1038/nature13423
|pmc=4278352 | pmid=24965652|bibcode=2014Natur.510..512D }}</ref>
⚫ In Figure 1, each circle corresponds to a PKS mutilifuctional protein, where ACP is ], KS is keto-ACP synthase, KSQ is a keto-ACP synthase like domain, AT is acyltransferase, KR is keto ACP reductase, KR with cross is inactive KR, DH is hydroxyl-thioester dehydratase, ER is enoyl reductase, TEI is thioesterase domain I, TEII is type II thioesterase.
<ref>{{cite journal <ref>{{cite journal
| author = D.L. Akey, J.D. Kittendorf, J.W. Giraldes, R.A. Fecik, D.H. Sherman, and J.L. Smith |author1=D.L. Akey |author2=J.D. Kittendorf |author3=J.W. Giraldes |author4=R.A. Fecik |author5=D.H. Sherman |author6=J.L. Smith |name-list-style=amp | year = 2006
| date = 2006 | pages = 537–542
| pages = 537-542
| volume = 2 | title = Structural basis for macrolactonization by the pikromycin thioesterase. | volume = 2 | title = Structural basis for macrolactonization by the pikromycin thioesterase.
| journal = Nature Chemical Biology | journal = Nature Chemical Biology
|issue=10 | doi=10.1038/nchembio824 | pmid=16969372
}}</ref>
|s2cid=6262508 }}</ref>
Des corresponds to the enzymes utilized in desosamine biosynthesis and transfer, which include DesI-DesVIII. Des corresponds to the enzymes utilized in desosamine biosynthesis and transfer, which include DesI-DesVIII.{{cn|date=March 2023}}


Figure 2 represents the desosamine deoxyamino sugar biosynthetic pathway. DesI-DesVI (des locus of pikromycin PKS) encodes all the enzymes needed to obtain TDP-desoamine from TDP-glucose. DesVII and DesVIII activities transfer desoamine to narbonolide and narbomycin is obtained. PikC cytochrome P450 hydrolase catalyzes the hydroxylation of narbomycin to obtain pikromycin. Figure 2 represents the desosamine deoxyamino sugar biosynthetic pathway. DesI-DesVI (des locus of pikromycin PKS) encodes all the enzymes needed to obtain TDP-desoamine from TDP-glucose. DesVII and DesVIII activities transfer desoamine to narbonolide and narbomycin is obtained. PikC cytochrome P450 hydrolase catalyzes the hydroxylation of narbomycin to obtain pikromycin.
<ref name="auto"/>
⚫ <ref>{{cite journal
| author = Y. Xue and D. Sherman
| date = 2001
| pages = 15-26
| volume = 3 | title = Biosynthesis and Combinatorial Biosynthesis of Pikromycin-Related Macrolides in Streptomyces venezuelae
⚫ | journal = Metabolic Engineering
| doi = 10.1006/mben.2000.0167
}}</ref>


] ]
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==See also== ==See also==
* ] *]
*]


==References== ==References==
<references/> <references/>




] ]