Ketosynthases in the Initiation and Elongation Modules of Aromatic Polyketide Synthases Have Orthogonal Acyl Carrier Protein Specificity†

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6588-6595 ◽  
Author(s):  
Yi Tang ◽  
Taek Soon Lee ◽  
Seiji Kobayashi ◽  
Chaitan Khosla

2013 ◽  
Vol 69 (12) ◽  
pp. 2340-2352 ◽  
Author(s):  
Karine Moncoq ◽  
Leslie Regad ◽  
Stéphane Mann ◽  
Annick Méjean ◽  
Olivier Ploux

Anatoxin-a and homoanatoxin-a are two potent cyanobacterial neurotoxins biosynthesized from L-proline by a short pathway involving polyketide synthases. Proline is first loaded onto AnaD, an acyl carrier protein, and prolyl-AnaD is then oxidized to 1-pyrroline-5-carboxyl-AnaD by a flavoprotein, AnaB. Three polyketide synthases then transform this imine into anatoxin-a or homoanatoxin-a. AnaB was crystallized in its holo form and its three-dimensional structure was determined by X-ray diffraction at 2.8 Å resolution. AnaB is a homotetramer and its fold is very similar to that of the acyl-CoA dehydrogenases (ACADs). The active-site base of AnaB, Glu244, superimposed very well with that of human isovaleryl-CoA dehydrogenase, confirming previous site-directed mutagenesis experiments and mechanistic proposals. The substrate-binding site of AnaB is small and is likely to be fitted for the pyrrolidine ring of proline. However, in contrast to ACADs, which use an electron-transport protein, AnaB uses molecular oxygen as the electron acceptor, as in acyl-CoA oxidases. Calculation of the solvent-accessible surface area around the FAD in AnaB and in several homologues showed that it is significantly larger in AnaB than in its homologues. A protonated histidine near the FAD in AnaB is likely to participate in oxygen activation. Furthermore, an array of water molecules detected in the AnaB structure suggests a possible path for molecular oxygen towards FAD. This is consistent with AnaB being an oxidase rather than a dehydrogenase. The structure of AnaB is the first to be described for a prolyl-ACP oxidase and it will contribute to defining the structural basis responsible for oxygen reactivity in flavoenzymes.



2006 ◽  
Vol 128 (9) ◽  
pp. 3067-3074 ◽  
Author(s):  
Alice Y. Chen ◽  
Nathan A. Schnarr ◽  
Chu-Young Kim ◽  
David E. Cane ◽  
Chaitan Khosla




2021 ◽  
Author(s):  
Munro Passmore ◽  
Angelo Gallo ◽  
Józef Romuald Lewandowski ◽  
Matthew Jenner

The biosynthesis of polyketides by type I modular polyketide synthases (PKS) relies on co-ordinated interactions between acyl carrier protein (ACP) domains and catalytic domains within the megasynthase. Despite the importance...



2003 ◽  
Vol 10 (5) ◽  
pp. 427-433
Author(s):  
P. Sasikumar ◽  
K. Kumar ◽  
V. Rajasekharan Pillai


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