title: Aspects of the biosynthesis of non-aromatic fungal polyketides by iterative polyketide synthases.
abstract: Lovastatin biosynthesis in Aspergillus terreus involves two unusual type I multifunctional polyketide syntheses (PKSs). Lovastatin nonaketide synthase (LNKS), the product of the lovB gene, is an iterative PKS that interacts with LovC, a putative enoyl reductase, to catalyze the 35 separate reactions in the biosynthesis of dihydromonacolin L, a lovastatin precursor. LNKS also displays Diels-Alderase activity in vitro. Lovastatin diketide synthase (LDKS) made by lovF, in contrast, acts non-iteratively like the bacterial modular PKSs to make (2R)-2-methylbutyric acid. Then, like LNKS, LDKS interacts closely with another protein, the LovD transesterase enzyme that catalyzes attachment of the 2-methylbutyric acid to monacolin J in the final step of the lovastatin pathway. Key features of the genes for these four enzymes and others, plus the regulatory and self-resistance factors involved in lovastatin production, are also described.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, USA. hutchinson@kosan.com
authors.forename: C R
authors.initials: CR
authors.lastname: Hutchinson
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
authors.forename: C
authors.initials: C
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Kendrew
authors.forename: K
authors.initials: K
authors.lastname: Auclair
authors.forename: J
authors.initials: J
authors.lastname: Vederas
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001230:Aspergillus / Q000201:enzymology* / Q000235:genetics; D008148:Lovastatin / Q000096:biosynthesis* / Q000235:genetics; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D009097:Multienzyme Complexes; D008148:Lovastatin