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This new volume of "Methods in Enzymology" continues the legacy of
this premier serial by containing quality chapters authored by
leaders in the field. Thethird of3 volumes covering Natural product
biosynthesis by microorganisms and plants.
This new volume of "Methods in Enzymology" continues the legacy of
this premier serial by containing quality chapters authored by
leaders in the field. The second of3 volumes covering Natural
product biosynthesis by microorganisms and plants.
This new volume of "Methods in Enzymology" continues the legacy of
this premier serial by containing quality chapters authored by
leaders in the field. The first of3 volumes covering Natural
product biosynthesis by microorganisms and plants, it has chapters
on such topics as Kinetics of plant sesquiterpene synthases,
Terpenoid biosynthesis in fungi, and plant Type III polyketide
synthases.
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.
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.
This is an insider's account of 50 years of genetic studies of the soil-inhabiting microbes that produce most of the antibiotics used to treat infections, as well as anti-cancer, anti-parasitic and immunosuppressant drugs. The book begins by describing how these microbes - the actinomycetes - were discovered in the latter part of the nineteenth century, but remained a 'Cinderella' group until, in the 1940s, they shot to prominence with the discovery of streptomycin, the first effective treatment for tuberculosis and only the second antibiotic after penicillin to become a medical marvel. There followed a massive effort over several decades to find further treatments for infectious diseases and cancer, tempered by the rise of antibiotic resistance consequent on antibiotic misuse and over-use. The book goes on to describe the discovery of gene exchange in the actinomycetes in the context of the rise of microbial genetics in the mid-20th century, leading to determination of the complete DNA sequence of a model member of the group at the turn of the millennium. There follow chapters in which the intricate molecular machinery that adapts the organisms' metabolism and development to life in the soil, including antibiotic production, is illuminated by the DNA blueprint. Then comes an up-to-the minute account of the use of genetic engineering to make novel, hybrid antibiotics and a topical description of techniques to learn the roles of the thousands of genes in a genome sequence, throwing a powerful light on the biology of the organisms and their harnessing for increasing antibiotic prductivity. In the final chapter we return to the mycobacteria that cause tuberculosis and leprosy, the first actinomycetes to be discovered, and how methodology, in part derived from the study of the streptomycetes, is being applied to understand and control these still deadly pathogens.
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