By D. I. Edwards
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This quantity is the 3rd within the sequence dedicated to Antibiotics initiated by way of Springer Verlag in 1967. the 1st volumes have been dedicated to the Mode of motion of Antibiotics and Biogenesis, respectively and have been bought graciously. in the course of the intervening years those works were used frequently by means of examine staff and scholars alike and feature been quoted commonly.
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Almost all the intermediates are bound presuma:bly to a multienzyme complex and are only released in the final stages. 2 Acetyl GoA - - - . , - Malonyl GoA r Acetoacetyl GoA Acetyl GoA Repeated condensations o o o o o Polyketomethyl chain I Ringlclosure , OH OH OH OH o 6-Methylpretetramide NH2 . - _ - - - - - - - - - , Oxidation Amination methylation and hydrogenation Amination, methylation and hydrogenation I + GI OH o OH Anhydro-7-chlorotetracylcine Hydroxylation GI OH tI Strep~o~yces aureofactenS H3 G , ........
36 ANTIMICROBIAL DRUG ACTION weigpt (102) of any antibiotic-it can be easily synthesised chemically and this is now the means by which the drug is manufactured. The chemical synthesis either starts from D-serine methyl ester or L-serine, both involving a five-stage conversion to the drug. D-Serine methyl ester is first converted to the triphenylmethyl derivative which, when heated with methane sulphonyl chloride, yields the ethyleneimine derivative which is converted to the corresponding hydroxamic acid with hydroxylamine and sodium methoxide.
Since a number of chemicals require to be activated by metabolism before the mutagen is formed, Ames and his colleagues introduced a modification in 1975 which enables such an activation to occur. This is achieved by incubating, on Petri dishes, the compounds to be tested, the S. typhimurium strains, an NADPH-gen- PRINCIPLES OF ANTIMICROBIAL DRUG ACTION 29 erating system, and a sub fraction of an induced liver homogenate designated the S9 microsomal mix. This enables a greatly increased number of chemical and drugs to be detected as mutagenic agents.
Antimicrobial Drug Action by D. I. Edwards