5ing: Difference between revisions
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==A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unit== | |||
<StructureSection load='5ing' size='340' side='right'caption='[[5ing]], [[Resolution|resolution]] 2.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ing]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_ambofaciens_ATCC_23877 Streptomyces ambofaciens ATCC 23877]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ING OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ING FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ing FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ing OCA], [https://pdbe.org/5ing PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ing RCSB], [https://www.ebi.ac.uk/pdbsum/5ing PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ing ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0ACI9_STRA7 A0ACI9_STRA7] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of alpha, beta-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual beta-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues. | |||
A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.,Ray L, Valentic TR, Miyazawa T, Withall DM, Song L, Milligan JC, Osada H, Takahashi S, Tsai SC, Challis GL Nat Commun. 2016 Dec 21;7:13609. doi: 10.1038/ncomms13609. PMID:28000660<ref>PMID:28000660</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ing" style="background-color:#fffaf0;"></div> | ||
[[Category: Miyazawa | == References == | ||
[[Category: Osada | <references/> | ||
[[Category: Ray | __TOC__ | ||
[[Category: Song | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Streptomyces ambofaciens ATCC 23877]] | ||
[[Category: | [[Category: Challis GL]] | ||
[[Category: | [[Category: Milligan JC]] | ||
[[Category: Miyazawa T]] | |||
[[Category: Osada H]] | |||
[[Category: Ray L]] | |||
[[Category: Song L]] | |||
[[Category: Takahashi S]] | |||
[[Category: Tsai SC]] | |||
[[Category: Valentic TR]] | |||
[[Category: Withall DM]] | |||
Latest revision as of 17:02, 30 August 2023
A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unitA crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unit
Structural highlights
FunctionPublication Abstract from PubMedType I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of alpha, beta-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual beta-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues. A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.,Ray L, Valentic TR, Miyazawa T, Withall DM, Song L, Milligan JC, Osada H, Takahashi S, Tsai SC, Challis GL Nat Commun. 2016 Dec 21;7:13609. doi: 10.1038/ncomms13609. PMID:28000660[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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