TY - JOUR
T1 - Use of Mutants in the Study of Aminocyclitol Antibiotic Biosynthesis and the Preparation of the Hybrimycin C Complex
AU - Shier, W. Thomas
AU - Schaefer, Phillip C.
AU - Gottlieb, David
AU - Rinehart, Kenneth L.
PY - 1974/12/1
Y1 - 1974/12/1
N2 - A technique previously used to isolate a mutant of Streptomyces fradiae capable of synthesizing the antibiotic neomycin only in the presence of the subunit 2-deoxystreptamine has been applied to S. rimosus forma paromomycinus and S. kanamyceticus to produce mutants capable of synthesizing paromomycin and kanamycin, respectively, only in the presence of added 2-deoxystreptamine subunit. Neamine, paromamine, and 6-kanosaminido-2-deoxystreptamine—2-deoxystreptamine-containing glycosides that are plausible intermediates in the biosynthesis of the three antibiotics—were also tested as substrates. The mutants studied did not convert the glycosides to active antibiotics. The mutant of 5. rimosus forma paromomycinus converts streptamine, an analog of 2-deoxystreptamine, to two new antibiotics, hybrimycins C1 and C2, analogs of paromomycins I and II, respectively, in which the only modification is that 2-deoxystreptamine has been replaced by streptamine. Selective hydrolysis yielded a third new antibiotic, hybrimycin C3, an analog of paromamine.
AB - A technique previously used to isolate a mutant of Streptomyces fradiae capable of synthesizing the antibiotic neomycin only in the presence of the subunit 2-deoxystreptamine has been applied to S. rimosus forma paromomycinus and S. kanamyceticus to produce mutants capable of synthesizing paromomycin and kanamycin, respectively, only in the presence of added 2-deoxystreptamine subunit. Neamine, paromamine, and 6-kanosaminido-2-deoxystreptamine—2-deoxystreptamine-containing glycosides that are plausible intermediates in the biosynthesis of the three antibiotics—were also tested as substrates. The mutants studied did not convert the glycosides to active antibiotics. The mutant of 5. rimosus forma paromomycinus converts streptamine, an analog of 2-deoxystreptamine, to two new antibiotics, hybrimycins C1 and C2, analogs of paromomycins I and II, respectively, in which the only modification is that 2-deoxystreptamine has been replaced by streptamine. Selective hydrolysis yielded a third new antibiotic, hybrimycin C3, an analog of paromamine.
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U2 - 10.1021/bi00722a002
DO - 10.1021/bi00722a002
M3 - Article
C2 - 4433510
AN - SCOPUS:0016287808
SN - 0006-2960
VL - 13
SP - 5073
EP - 5078
JO - Biochemistry
JF - Biochemistry
IS - 25
ER -