Complex enzymes in microbial natural product biosynthesis, Part A: overview articles and peptidesEdited by
- David Hopwood, John Innes Centre and AFRC Institute of Plant Science Research, Norwich, UK
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.
Researchers in cell, molecular and developmental biology; biochemists, pharmacologists, geneticists.
Methods in Enzymology
Hardbound, 350 Pages
Published: April 2009
Imprint: Academic Press
- Part 1: Overview articlesIntroduction - chemical classes of complex natural products and overview of their biosynthesisDiscovery of novel natural productsTrans-modification of intermediates on the assembly line in PKS, FAS and NRPS biosynthesisPost-assembly line modifications, including glycosylationCloning and analysis of natural product pathwaysIn silico prediction of pathways from DNA sequenceMass spectrometric analysis of PKS and NRPS biosynthetic intermediatesSynthetic probes for PKS and NRPS biochemistryDirected evolution of natural productsExpression in a heterologous hostPathway-specific and global regulation of antibiotic biosynthesis: Regulation of antibiotic production by bacterial hormones:Part 2: PeptidesA. Non-ribosomally-synthesised peptidesOverview of NRPSs, and mechanistic and structural studiesSiderophoresCephamycins and clavulanic acidGlycopeptidesLipopeptidesPrecursor BiosynthesisB. Ribosomally synthesised peptidesLantibiotic biosynthesis and engineering of novel compoundsCyclic peptides from marine bacteria