Priming Type II Polyketide Synthases Via a Type II Nonribosomal Peptide Synthetase Mechanism
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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.
Lee W, Choi S, Jang A, Son K, Kim Y Sci Rep. 2021; 11(1):7945.
PMID: 33846444 PMC: 8041823. DOI: 10.1038/s41598-021-86997-3.
Kim M, Winter J, Asolkar R, Boonlarppradab C, Cullum R, Fenical W J Org Chem. 2021; 86(16):11140-11148.
PMID: 33844925 PMC: 8383307. DOI: 10.1021/acs.joc.1c00262.
Cell-free synthetic biology for biosynthesis of pharmaceutical natural products.
Li J, Zhang L, Liu W Synth Syst Biotechnol. 2018; 3(2):83-89.
PMID: 29900420 PMC: 5995452. DOI: 10.1016/j.synbio.2018.02.002.
Sala G, Hochmuth T, Costantino V, Teta R, Gerwick W, Gerwick L Environ Microbiol Rep. 2013; 5(6):809-18.
PMID: 24249289 PMC: 3908369. DOI: 10.1111/1758-2229.12081.
Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement.
Teufel R, Miyanaga A, Michaudel Q, Stull F, Louie G, Noel J Nature. 2013; 503(7477):552-556.
PMID: 24162851 PMC: 3844076. DOI: 10.1038/nature12643.