Proposed arrangement of proteins forming a bacterial type II polyketide synthase.
Aklanonic acid is synthesized by a type II polyketide synthase (PKS) composed of eight protein subunits. The network of protein interactions within this complex was investigated using a yeast two-hybrid system, by coaffinity chromatography and by two different computer-aided protein docking simulations. Results suggest that the ketosynthase (KS) alpha and beta subunits interact with each other, and that the KSalpha subunit also probably interacts with a malonyl-CoA:ACP acyltransferase (DpsD), forming a putative minimal synthase. We speculate that DpsD may physically inhibit the priming reaction, allowing the choice of propionate rather than acetate as the starter unit. We also suggest a structural role for the cyclase (DpsY) in maintaining the overall structural integrity of the complex.
Castaldo
Gaetano
G
School of Pharmacy, University of London, 29-39 Brunswick Square, Bloomsbury, London WC1N 1AX, UK.
Zucko
Jurica
J
Heidelberger
Sibylle
S
Vujaklija
Dusica
D
Hranueli
Daslav
D
Cullum
John
J
Wattana-Amorn
Pakorn
P
Crump
Matthew P
MP
Crosby
John
J
Long
Paul F
PF
D000880:Anthraquinones / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002846:Chromatography, Affinity; D003198:Computer Simulation; D008958:Models, Molecular; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D020798:Two-Hybrid System Techniques
D000880:Anthraquinones; D001426:Bacterial Proteins; D048630:Polyketide Synthases; C042374:aklanonic acid