Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis.
Polyketides, the ubiquitous products of secondary metabolism in microorganisms, are made by a process resembling fatty acid biosynthesis that allows the suppression of reduction or dehydration reactions at specific biosynthetic steps, giving rise to a wide range of often medically useful products. The lovastatin biosynthesis cluster contains two type I polyketide synthase genes. Synthesis of the main nonaketide-derived skeleton was found to require the previously known iterative lovastatin nonaketide synthase (LNKS), plus at least one additional protein (LovC) that interacts with LNKS and is necessary for the correct processing of the growing polyketide chain and production of dihydromonacolin L. The noniterative lovastatin diketide synthase (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts closely with an additional transesterase (LovD) responsible for assembling lovastatin from this polyketide and monacolin J.
Kennedy
J
J
School of Pharmacy, Bacteriology Department, University of Wisconsin, Madison, WI 53706, USA.
Auclair
K
K
Kendrew
S G
SG
Park
C
C
Vederas
J C
JC
Hutchinson
C R
CR
D001230:Aspergillus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002087:Butyrates / Q000378:metabolism; D004950:Esterases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D005800:Genes, Fungal; D008148:Lovastatin / Q000096:biosynthesis*; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism
D002087:Butyrates; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D009281:Naphthalenes; C045373:dihydromonacolin L; D008148:Lovastatin; D004950:Esterases; C045376:monacolin J; C019475:2-methylbutanoic acid