The Biosynthesis of Tetracycline Antibiotics

Biosynthesis of the Tetracycline Antibiotics

“…The same result was obtained independently by Miller et al (21). Birch, Snell, and Thompson (22,23) and Gatenbeck (24) subsequently were able to show by degradation studies that the carbon atoms were indeed derived from acetate carboxyl and methyl in an alternating sequence although, because of experimental difficulties, complete degradation of the tetracyclines to isolate every carbon atom for absolutely rigorous proof has…”

“…A secondary metabolite may be defined as a substance with no presently apparent utility (such as structure, energy, reproduction, growth, e k ) to the producing organism and which is elaborated, usually, when the primary growth and replication still not been accomplished. The C-and Nmethyl groups are derived from methionine (21,22,25) as expected, and the nitrogen atom at CS likely comes from glutamic acid. Certain tetracyclines (I, IV, V, VIII) have a chlorine atom a t C,.…”

“…Glutamate had no specific promoting effect over the other Krebs cycle acids tested. Using the data of Birch and Snell (22,23) and Gatenbeck's hypothesis (24), i t is possible to achieve an excellent fit for the experimental data (Scheme VII).…”

“…An interesting theory which has not been entirely abandoned (14) suggested that the majority of Ring A of oxytetracycline was derived from a glutamine unit. This ingenious idea would require the involvement of hypothetical polyketide XXVII, and was advanced prior to the recognition of the role of malonate in polyketide biosynthesis (22,23). Having noticed that the amount of H0,C CONH,…”

Biogenesis of Variotin

“…The C13-hydroxy acid moiety might arise by the head-to-tail condensation of 6 acetic acid units.' SNELL, BIRCH and THOMsoN (9,10) demonstrated that oxytetracycline, biosynthesized in the presence of 14CH3CO2H, Me-14C-methionine, and glutamic acid-2-14C, contained C-Me and N-Me2 derived from methionine and the main skeleton was built up by 7 acetic acid units and a unit of glutamate.…”