Actinomycete metabolism. Incorporation of 14C-labelled compounds into streptomycin

Hunter, G. D.; Hockenhull, D. J. D.

doi:10.1042/bj0590268

Cited by 37 publications

(13 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conversion by a S. griseus suspension of 'ICO2 to arginine labeled in the guanidino group was demonstrated a few years later (11 1). In 1955, Hunter and Hockenhull (59) reported that 14C glucose entered each of the three moieties of streptomycin to an equal extent but that the guanidino carbons were only poorly labeled. They further found that streptamine was not a true precursor since labeled streptamine entered all three moieties of the streptomycin molecule, the streptidine portion becoming no more radioactive than the other portions.…”

Section: )mentioning

confidence: 99%

Biochemistry and regulation of streptomycin and mannosidostreptomycinase (alpha-D-mannosidase) formation.

Demain¹,

Inamine²

1970

Bacteriological Reviews

View full text Add to dashboard Cite

show abstract

Section: )mentioning

confidence: 99%

Biochemistry and regulation of streptomycin and mannosidostreptomycinase (alpha-D-mannosidase) formation.

Demain¹,

Inamine²

1970

Bacteriological Reviews

View full text Add to dashboard Cite

show abstract

“…The name highlights the fact that these antibiotics, in addition to an array of variously modified amino-sugars, contain an unusual cyclohexane derivative which can either be hexa-substituted as the streptamine unit (1) of streptomycin or penta-substituted as the 2-deoxystreptamine ring (2). The latter unit is present in neomycin (3) and more than fifty other related antibiotics.…”

mentioning

confidence: 99%

Neomycin biosynthesis: The incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis.

Goda

Akhtar

1992

J. Antibiot.

View full text Add to dashboard Cite

D-[6-3H3]6-Deoxy-5-ketoglucose(10) and D-[5,6-3H2]6-deoxyglucose (ll) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. D-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor D-glucose, and wasfound to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the previous proposals that in the formation of 2-deoxystreptamine the C-6 hydroxyl group of D-glucose is removed prior to the cyclisation reaction. Studies using the incorporation of d-[3-3H]glucose, D-[3,4-3H2]glucose and D-[5-3H]glucose into neomycin followed by the degradation of the latter established that in the biosynthesis of the 2-deoxystreptamine ring the C-4 and C-5 hydrogen atoms of glucose are removed. The loss of the C-4 hydrogen atom of the glucose is attributed to the formation of a 4-keto derivative which facilitates the removal of the C-5 hydrogen atom thus setting the stage for the expulsion of the C-6 hydroxyl group. The 5,6-olefinic intermediate formed in the process then undergoes cyclisation eventually releasing 2-deoxyinosose. The enzyme systems which participate in the conversion of D-glucose equivalent into 2-deoxyinosose may be described as 2-deoxyinosose synthase that in broad mechanistic terms resembles dehydroquinate synthase.A large group of clinically useful antibiotics, to which streptomycin and neomycin belong, are classified as aminoglycoside-aminocyclitol antibiotics. The name highlights the fact that these antibiotics, in addition to an array of variously modified amino-sugars, contain an unusual cyclohexane derivative which can either be hexa-substituted as the streptamine unit (1) of streptomycin or penta-substituted as the 2-deoxystreptamine ring (2). The latter unit is present in neomycin (3) and more than fifty other related antibiotics. It is now knownthat the carbon skeletons of both types of aminocyclitols (1 and 2) arise from D-glucose1>2) and the elegant studies of Walker and Walker3) have established that, in the formation of the streptamine ring system of streptomycin, the key event is the inositol synthase catalysed cyclisation of glucose 6-phosphate into inositol 1-phosphate, Scheme 2. The latter, through a multistage process, is then converted into streptidine (this is a diguanidinated derivative of 1). The knowledge of the latter biosynthesis provided the stimulus to consider the possibility that a cyclisation process similar to that shown in Scheme 2, followed by the reductive removal of the unwanted hydroxyl group, may also be involved in the formation of 2-deoxystreptamine. Gradually however observations were made which questioned this hypothesis and suggested that the two aminocyclitols (1 and 2) may be synthesised by two entirely different mechanisms. For example, the patterns for the incorporation of the C-skeleton ofD-glucose f Present address:

show abstract

“…KAROW et al (1952) ftrst reported the preparation of 14C_la_ beled streptomycin by feeding labeled glucose or starch to the growing culture of S.griseus, then HUNTER and HOCKENHULL (1955) found that about 5% of D-[14C]glucose supplied to a 60-h culture of S. griseus was incorporated into streptomycin with the radioactivity equally distributed into the three subunits (streptidine, 34.1 %; streptose, 31.7%; and N-methyl-L-glucosamine, 34.8%). Thereafter, 14C-labeled compounds were used extensively as discussed in review articles by HOCKENHULL (1960), MENDICINO and PICKEN (1966), HORNER (1967), AKAMATSU (1968), andINAMINE (1970).…”

Section: Streptomycin and Bluensomycinmentioning

confidence: 99%

“…The mechanism remained obscure until recently. HUNTER and HOCKENHULL (1955) observed that 15.5% of N-methy1-L-[U-14C]glucosamine added to a 60-hr culture of S.griseus was incorporated into streptomycin, and about 75% of the incorporated radioactivity was found in the Nmethyl-L-glucosamine moiety. Incorporation of D-[U-14 C]glucose was very low (5%).…”

Section: B) Streptosementioning

confidence: 99%

Biosynthesis and Mutasynthesis of Aminoglycoside Antibiotics

Okuda¹,

Ito²

1982

Handbook of Experimental Pharmacology

View full text Add to dashboard Cite

Actinomycete metabolism. Incorporation of 14C-labelled compounds into streptomycin

Cited by 37 publications

References 5 publications

Biochemistry and regulation of streptomycin and mannosidostreptomycinase (alpha-D-mannosidase) formation.

Biochemistry and regulation of streptomycin and mannosidostreptomycinase (alpha-D-mannosidase) formation.

Neomycin biosynthesis: The incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis.

Biosynthesis and Mutasynthesis of Aminoglycoside Antibiotics

Contact Info

Product

Resources

About