Complex Enzymes in Microbial Natural Product Biosynthesis, Part B: Polyketides, Aminocoumarins and Carbohydrates

This volume will showcase the most important chemical classes of complex enzymes, which have been an important traditional source of valuable antibiotics and other drugs.

David A. Hopwood (Volume editor)

9780123745910, Elsevier Science

Hardback, published 2 June 2009

398 pages
22.9 x 15.1 x 2.6 cm, 1.16 kg

Microbial natural products have been an important traditional source of valuable antibiotics and other drugs but interest in them waned in the 1990s when big pharma decided that their discovery was no longer cost-effective and concentrated instead on synthetic chemistry as a source of novel compounds, often with disappointing results. Moreover understanding the biosynthesis of complex natural products was frustratingly difficult. With the development of molecular genetic methods to isolate and manipulate the complex microbial enzymes that make natural products, unexpected chemistry has been revealed and interest in the compounds has again flowered. This two-volume treatment of the subject will showcase the most important chemical classes of complex natural products: the peptides, made by the assembly of short chains of amino acid subunits, and the polyketides, assembled from the joining of small carboxylic acids such as acetate and malonate. In both classes, variation in sub-unit structure, number and chemical modification leads to an almost infinite variety of final structures, accounting for the huge importance of the compounds in nature and medicine.

Part 1: Polyketides

Overview of polyketide biosynthesis

A) Type I

Structural studies

i) Iterative

Fungal PKSs/FASs
Polyunsaturated fatty acids (PUFAs)
Enediynes

ii) Modular

Macrolides as a paradigm
Macrolides - skipping and stuttering of modules
Trans-AT class
Polyethers
Polyenes
Polyketides in mycobacteria
Docking of subunits
Novel polyketides by genetic engineering
De novo synthesis of pathway genes
Precursor biosynthesis

B) Type II

In vitro analysis and engineering of novel compounds
Bacterial fatty acid biosynthesis

C) Type III

In vitro / in vivo biochemical studies
Structural studies

Part 2: Terpenoids

Enzymology and structural biology of terpenoid biosynthesis

Part 3: Aminocoumarins

Part 4: Carbohydrates

Aminoglycosides
Deoxysugar biosynthesis

Subject Areas: Enzymology [PSBZ], Biochemistry [PSB], Biophysics [PHVN], Pharmacology [MMG]