Priming type II polyketide synthases via a type II nonribosomal peptide synthetase mechanism.
Benzoic acid priming of the enterocin and actinorhodin type II polyketide synthase complexes was accomplished in vitro via an unprecedented type II nonribosomal peptide synthetase-like mechanism involving the benzoate:acyl carrier protein (ACP) ligase EncN and the ACP EncC. The transfer of the aryl acid to the ACP is ATP-dependent, yet coenzyme A-independent, as characterized with radiolabeled substrates and protein mass spectrometry. Subsequent transport of the ACP-bound aryl group to the native enterocin and the aberrant actinorhodin ketosynthase chain length factor heterodimers was further demonstrated, thereby demonstrating the potential of this biocatalyst for engineering diverse aryl-primed aromatic polyketide agents.
Izumikawa
Miho
M
College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Cheng
Qian
Q
Moore
Bradley S
BS
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism; D009279:Naphthacenes / Q000737:chemistry / Q000378:metabolism; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D000095622:Benzoisochromanequinones
D000213:Acyl Carrier Protein; D000880:Anthraquinones; D003065:Coenzyme A; D009279:Naphthacenes; D010453:Peptide Synthases; D048630:Polyketide Synthases; C080889:5838 DNI; C104385:non-ribosomal peptide synthase; C013390:actinorhodin; D000095622:Benzoisochromanequinones