Pikromycin
title: "Pikromycin" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["macrolide-antibiotics"] topic_path: "general/macrolide-antibiotics" source: "https://en.wikipedia.org/wiki/Pikromycin" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 450797983 | ImageFile =Pikromycin.svg | ImageSize = | IUPACName = (3R,5R,6S,7S,9R,11E,13S,14R)-14-Ethyl-13-hydroxy-3,5,7,9,13-pentamethyl-6-[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyloxy]-1-oxacyclotetradec-11-ene-2,4,10-trione | SystematicName = (3R,5R,6S,7S,9R,11E,13S,14R)-6-{[(2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-13-hydroxy-3,5,7,9,13-pentamethyl-1-oxacyclotetradec-11-ene-2,4,10-trione | OtherNames = Picromycin |Section1={{Chembox Identifiers | CASNo_Ref = | CASNo = 19721-56-3 | UNII_Ref = | UNII = FBM8G3Z439 | PubChem = 5282037 | ChemSpiderID_Ref = | ChemSpiderID = 4445267 | ChEBI_Ref = | ChEBI = 29665 | StdInChI_Ref = | 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 = | StdInChIKey = UZQBOFAUUTZOQE-VSLWXVDYSA-N | SMILES = O=C2C@@HC | 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 | C=28 | H=47 | N=1 | O=8 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt =
Pikromycin was studied by Brokmann and Hekel in 1951 and was the first antibiotic macrolide to be isolated.{{cite journal |author1=Brockmann, H. |author2=Henkel, W. |name-list-style=amp | year = 1951 | pages = 184–288 | volume = 84 | title = Pikromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten | journal = Ntibiotica aus Actinomyceten | doi = 10.1002/cber.19510840306 Pikromycin is synthesized through a type I polyketide synthase system in Streptomyces venezuelae, a species of Gram-positive bacterium in the genus Streptomyces.{{cite journal |author1=Y. Xue |author2=D. Sherman |name-list-style=amp | year = 2001 | pages = 15–26 | volume = 3 | title = Biosynthesis and Combinatorial Biosynthesis of Pikromycin-Related Macrolides in Streptomyces venezuelae | journal = Metabolic Engineering |issue=1 | doi = 10.1006/mben.2000.0167 |pmid=11162229 Pikromycin is derived from narbonolide, a 14-membered ring macrolide. | author = Maezawa, T. Hori, A. Kinumaki and M. Suzuki | year = 1973 | pages = 771–775 | volume = 26 | title = Biological conversion of narbonolide to picromycin | journal = The Journal of Antibiotics | issue = 12 | doi = 10.7164/antibiotics.26.771 | pmid = 4792390 | doi-access= free 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 erythromycins and new epothilones. |author1=J.D. Kittendorf |author2=D.H. Sherman |name-list-style=amp | year = 2009 | pages = 2137–2146 | volume = 17 | title = The Methymycin/Pikromycin Biosynthetic Pathway: A Model for Metabolic Diversity in Natural Product | journal = Bioorg Med Chem |issue=6 | doi = 10.1016/j.bmc.2008.10.082 |pmc=2843759 | pmid=19027305}} TOC
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 terminated the biosynthetic procedure. |author1=S. Guptaa |author2=V. Lakshmanan |author3=B.S. Kima |author4=R. Fecik |author5=K. A. Reynolds |name-list-style=amp | year = 2008 | pages = 1609–1616 | volume = 9 | title = Generation of Novel Pikromycin Antibiotic Products Through Mutasynthesis | journal = ChemBioChem |issue=10 | doi = 10.1002/cbic.200700635 |pmc=2614871 | pmid=18512859}} 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. |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 }} 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=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 | pages = 537–542 | volume = 2 | title = Structural basis for macrolactonization by the pikromycin thioesterase. | journal = Nature Chemical Biology |issue=10 | doi=10.1038/nchembio824 | pmid=16969372 |s2cid=6262508 }} Des corresponds to the enzymes utilized in desosamine biosynthesis and transfer, which include DesI-DesVIII.
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[src="https://upload.wikimedia.org/wikipedia/commons/3/33/PikromycinPKS.png" caption="Figure 1: Domain organization of PKS for Narbonolide, a precursor of Pikromycin"] ::
::figure[src="https://upload.wikimedia.org/wikipedia/commons/9/92/Pikromycin2.png" caption="Figure 2: Pikromycin Formation through the desosamine deoxyamino sugar biosynthetic pathway"] ::
References
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