Complex Enzymes in Microbial Natural Product Biosynthesis, Part A: Overview Articles and Peptides

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: Overview articles

Introduction - chemical classes of complex natural products and overview of their biosynthesis
Discovery of novel natural products
Trans-modification of intermediates on the assembly line in PKS, FAS and NRPS biosynthesis
Post-assembly line modifications, including glycosylation
Cloning and analysis of natural product pathways
In silico prediction of pathways from DNA sequence
Mass spectrometric analysis of PKS and NRPS biosynthetic intermediates
Synthetic probes for PKS and NRPS biochemistry
Directed evolution of natural products
Expression in a heterologous host
Pathway-specific and global regulation of antibiotic biosynthesis:
Regulation of antibiotic production by bacterial hormones:

Part 2: Peptides

A. Non-ribosomally-synthesised peptides

Overview of NRPSs, and mechanistic and structural studies
Siderophores
Cephamycins and clavulanic acid
Glycopeptides
Lipopeptides
Precursor Biosynthesis

B. Ribosomally synthesised peptides

Lantibiotic biosynthesis and engineering of novel compounds
Cyclic peptides from marine bacteria

Researchers in cell, molecular and developmental biology; biochemists, pharmacologists, geneticists.