A singular enzymatic megacomplex from Bacillus subtilis.
Nonribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS are of particular interest, because they produce numerous therapeutic agents, have great potential for engineering novel compounds, and are the largest enzymes known. The predicted masses of known enzymatic assembly lines can reach almost 5 megadaltons, dwarfing even the ribosome (approximately 2.6 megadaltons). Despite their uniqueness and importance, little is known about the organization of these enzymes within the native producer cells. Here we report that an 80-kb gene cluster, which occupies approximately 2% of the Bacillus subtilis genome, encodes the subunits of approximately 2.5 megadalton active hybrid NRPS/PKS. Many copies of the NRPS/PKS assemble into a single organelle-like membrane-associated complex of tens to hundreds of megadaltons. Such an enzymatic megacomplex is unprecedented in bacterial subcellular organization and has important implications for engineering novel NRPS/PKSs.
Straight
Paul D
PD
Department of Microbiology and Molecular Genetics and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Fischbach
Michael A
MA
Walsh
Christopher T
CT
Rudner
David Z
DZ
Kolter
Roberto
R
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics; D020285:Cryoelectron Microscopy; D008969:Molecular Sequence Data; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics*; D048630:Polyketide Synthases / Q000235:genetics*; D015202:Protein Engineering
D048630:Polyketide Synthases; D010453:Peptide Synthases