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Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis.
TLDR
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 that interacts with LNKS and is necessary for the correct processing of the growing polyketide chain and production of dihydromonacolin L. Expand
The structure of ActVA‐Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis
TLDR
This is the first crystal structure of an enzyme involved in the tailoring of a type II aromatic polyketide and illustrates some of the enzyme–substrate recognition features that may apply to a range of other enzymes involved in modifying apolyketide core structure. Expand
Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate
TLDR
FkbO, RapK, Hyg5, and Bra8 are founder members of a previously unrecognized family of enzymes acting on chorismate, which includes the product of the bra8 gene from the pathway to the terpenoid natural product brasilicardin. Expand
Identification of a Flavin:NADH Oxidoreductase Involved in the Biosynthesis of Actinorhodin
TLDR
The subunit structure of the enzyme was investigated by analytical ultracentrifugation, which showed the protein to exist in rapid equilibrium between monomer and dimer forms, and the possible role of this oxidoreductase in the oxidative chemistry of actinorhodin biosynthesis is discussed. Expand
Identification of a monooxygenase from Streptomyces coelicolor A3(2) involved in biosynthesis of actinorhodin: purification and characterization of the recombinant enzyme.
TLDR
Site-directed mutagenesis was used to investigate the role of histidine residues thought to be important in the reaction; mutants lacking His-52 displayed much-reduced activity, consistent with the proposed mechanistic hypothesis that this histidine acts as a general base during catalysis. Expand
Investigating the Structural Plasticity of a Cytochrome P450
TLDR
Analysis of three-dimensional structures of a monomeric cytochrome P450 from Saccharopolyspora erythraea and the binding kinetics to its physiological ligand demonstrated that EryK binds erystromycin D via a mechanism involving at least two steps, confirmed that this complex scenario arises from a pre-existing equilibrium between the open and closed subpopulations of Eryk. Expand
Substrate specificity of the acyl transferase domains of EpoC from the epothilone polyketide synthase.
TLDR
To investigate this possibility the AT domains from modules 2 and 3 of the epothilone PKS were examined in the heterologous DEBS1-TE model PKS and, as expected, epoAT3 was significantly more promiscuous in keeping with its nature during epothILone biosynthesis. Expand
Engineering of complex polyketide biosynthesis — insights from sequencing of the monensin biosynthetic gene cluster
TLDR
The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic evidence for the mechanism of oxidative cyclisation through which polyethers such as monens in are formed from the uncyclised products of the PKS. Expand
DnrD cyclase involved in the biosynthesis of doxorubicin: purification and characterization of the recombinant enzyme.
TLDR
Understanding of the mechanism and active site topology of these proteins will allow one to determine the substrate and mechanistic parameters that are important for aromatic ring formation and in the future, these parameters may be able to be applied to some of the earlier polyketide cyclization processes that currently are difficult to study in vitro. Expand
Active-site residue, domain and module swaps in modular polyketide synthases
TLDR
A cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae is described and its use in domain and module swaps is demonstrated. Expand
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