A new modular polyketide synthase in the erythromycin producer Saccharopolyspora erythraea.
A previously unidentified set of genes encoding a modular polyketide synthase (PKS) has been sequenced in Saccharopolyspora erythraea, producer of the antibiotic erythromycin. This new PKS gene cluster (pke) contains four adjacent large open reading frames (ORFs) encoding eight extension modules, flanked by a number of other ORFs which can be plausibly assigned roles in polyketide biosynthesis. Disruption of the pke PKS genes gave S. erythraea mutant JC2::pSBKS6, whose growth characteristics and pattern of secondary metabolite production did not apparently differ from the parent strain under any of the growth conditions tested. However, the pke PKS loading module and individual pke acyltransferase domains were shown to be active when used in engineered hybrid PKSs, making it highly likely that under appropriate conditions these biosynthetic genes are indeed expressed and active, and synthesize a novel polyketide product.
Boakes
Steven
S
Cambridge Centre for Molecular Recognition and Department of Biochemistry, University of Cambridge, Cambridge, UK.
Oliynyk
Markiyan
M
Cortés
Jesús
J
Böhm
Ines
I
Rudd
Brian A M
BA
Revill
W Peter
WP
Staunton
Jim
J
Leadlay
Peter F
PF
D000213:Acyl Carrier Protein / Q000235:genetics; D004917:Erythromycin / Q000096:biosynthesis* / Q000737:chemistry; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics; D010441:Peptide Chain Elongation, Translational / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics*; D016930:Saccharopolyspora / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D000213:Acyl Carrier Protein; D009097:Multienzyme Complexes; D004917:Erythromycin; D048630:Polyketide Synthases