How Long to Read Cyclization and Reduction of Polyketides

How Long Does it Take to Read Cyclization and Reduction of Polyketides?

It takes the average reader 4 hours and 11 minutes to read Cyclization and Reduction of Polyketides by Brian Douglas Ames

Assuming a reading speed of 250 words per minute. Learn more

Description

Polyketides are a class of natural products with diverse chemical structures and important biological activities. The biosynthetic enzymes, acyl-CoA precursors, and chemical reactions that produce polyketides are similar to those used in fatty acid biosynthesis. However, the biosynthetic logic of fatty acid synthase (FAS) versus polyketide synthase (PKS) affords vastly different end products: while FAS yields fully-reduced, aliphatic products, PKS produces a diverse array of molecular scaffolds that are often highly derivatized chemically. A central question underlying research into polyketide biosynthesis is how PKS can precisely control chain elongation, functional-group modification, cyclization, and tailoring reactions to accomplish such product diversity. The objective of this dissertation is to understand: 1) the regiospecific cyclization of an unreduced polyketide chain by the Type II PKS aromatase/cyclase (ARO/CYC) for aromatic polyketide biosynthesis, and 2) the substrate specificity of the trans-acting enoyl reductase LovC (iterative Type I PKS) for the biosynthesis of the cholesterol-lowering drug lovastatin. The crystal structures and functional analyses of three PKS ARO/CYCs are reported. The ARO/CYC possesses a helix-grip fold characterized by the presence of a large, solvent-accessible interior pocket. Co-crystal structures demonstrate that the interior pocket of ARO/CYC can bind polyketides, while docking simulations of putative biosynthetic intermediates illustrates how the ARO/CYC pocket may influence cyclization specificity and catalyze intramolecular aldol condensation. Mutations to pocket residues were assayed by reconstituting polyketide biosynthesis, demonstrating that the interior pocket of ARO/CYC is critical for polyketide cyclization. The crystal structure of LovC shows that it is a unique monomeric medium-chain dehydrogenase/reductase (MDR) family member. We developed an in vitro activity assay to prove that LovC is enzymatically active as a standalone protein. Corresponding to the observed substrate specificity of LovC in vivo, the synthesis and testing of surrogate substrates showed that LovC does not reduce the shorter-chain diketide or triketide compounds, but does reduce the alpha-beta unsaturated tetraketide mimic, (E)-2-octenoyl-N-acetylcysteamine. LovC structural analysis, activity assays, and substrate docking suggest that the LovC active site can effectively discriminate between intermediates to selectively reduce three out of six possible intermediates during lovastatin biosynthesis.

How long is Cyclization and Reduction of Polyketides?

Cyclization and Reduction of Polyketides by Brian Douglas Ames is 246 pages long, and a total of 62,976 words.

This makes it 83% the length of the average book. It also has 77% more words than the average book.

How Long Does it Take to Read Cyclization and Reduction of Polyketides Aloud?

The average oral reading speed is 183 words per minute. This means it takes 5 hours and 44 minutes to read Cyclization and Reduction of Polyketides aloud.

What Reading Level is Cyclization and Reduction of Polyketides?

Cyclization and Reduction of Polyketides is suitable for students ages 12 and up.

Note that there may be other factors that effect this rating besides length that are not factored in on this page. This may include things like complex language or sensitive topics not suitable for students of certain ages.

When deciding what to show young students always use your best judgement and consult a professional.

Where Can I Buy Cyclization and Reduction of Polyketides?

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