Salinipyrone and Pacificanone Are Biosynthetic By-products of the Rosamicin Polyketide Synthase.
Salinipyrones and pacificanones are structurally related polyketides from Salinispora pacifica CNS-237 that are proposed to arise from the same modular polyketide synthase (PKS) assembly line. Genome sequencing revealed a large macrolide PKS gene cluster that codes for the biosynthesis of rosamicin A and a series of new macrolide antibiotics. Mutagenesis experiments unexpectedly correlated salinipyrone and pacificanone biosynthesis to the rosamicin octamodule Spr PKS. Remarkably, this bifurcated polyketide pathway illuminates a series of enzymatic domain- and module-skipping reactions that give rise to natural polyketide product diversity. Our findings enlarge the growing knowledge of polyketide biochemistry and illuminate potential challenges in PKS bioengineering.
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).|Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Takayoshi
T
Awakawa
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).
Max
M
Crüsemann
Pediatrics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).
Jason
J
Munguia
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).
Nadine
N
Ziemert
Pediatrics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).
Victor
V
Nizet
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).
William
W
Fenical
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA). bsmoore@ucsd.edu.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA). bsmoore@ucsd.edu.
Bradley S
BS
Moore
D039903:Actinobacteria / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D053898:Biosynthetic Pathways; D003512:Cyclohexanones / Q000378:metabolism*; D007933:Leucomycins / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D048630:Polyketide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011753:Pyrones / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003512:Cyclohexanones; D007933:Leucomycins; D011753:Pyrones; C529468:pacificanone A; C529466:salinipyrone A; D048630:Polyketide Synthases; C060286:rosaramicin
Salinispora; biosynthesis; macrolide antibiotics; polyketide synthases