Biosynthesis of butirosins. II. Biosynthetic pathway of butirosins elucidated from cosynthesis and feeding experiments.

Furumai, Tamotsu; Takeda, Katsuo; Kinumaki, Akio; Ito, Yukio; Okuda, Tomoharu

doi:10.7164/antibiotics.32.891

Cited by 38 publications

(35 citation statements)

References 22 publications

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“…10 Cosynthesis with blocked mutants was also effective to determine the order of biosynthetic steps. 11 However, these experiments yielded no direct evidence for enzymatic reaction mechanisms.…”

Section: Introductionmentioning

confidence: 94%

Biosynthetic genes for aminoglycoside antibiotics

Kudo

Eguchi

2009

J Antibiot

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Biosynthetic studies of aminoglycoside antibiotics have progressed remarkably during the last decade. Many biosynthetic gene clusters for aminoglycoside antibiotics including streptomycin, kanamycin, butirosin, neomycin and gentamicin have been identified to date. In addition, most butirosin and neomycin biosynthetic enzymes have been functionally characterized using recombinant proteins. Herein, we reanalyze biosynthetic genes for structurally related 2-deoxystreptamine (2DOS)-containing aminoglycosides, such as kanamycin, gentamicin and istamycin, based on genetic information including characterized biosynthetic enzymes in neomycin and butirosin biosynthetic pathways. These proposed enzymatic functions for uncharacterized enzymes are expected to support investigation of the complex biosynthetic pathways for this important class of antibiotics.

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Section: Introductionmentioning

confidence: 94%

Biosynthetic genes for aminoglycoside antibiotics

Kudo

Eguchi

2009

J Antibiot

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“…Concerning to the biosynthesis of butirosin, isotopefeeding experiments and cosynthesis methods using blocked mutants allowed to elucidate the gross biosynthetic pathway [8,9]. More recently, a significant part of the butirosin biosynthetic gene cluster has been identified from Bacillus circulans SANK 72073 through the discovery of the protein (BtrC) and of the gene (btrC ) for 2-deoxyscyllo-inosose synthase, which catalyzes the key carbocyclization of glucose-6-phosphate in the pathway for DOS (Scheme 1) [10ϳ12].…”

Section: Introductionmentioning

confidence: 99%

Extended Sequence and Functional Analysis of the Butirosin Biosynthetic Gene Cluster in Bacillus circulans SANK 72073

et al. 2005

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Butirosin produced by Bacillus circulans is among the clinically important 2-deoxystreptamine containing aminoglycoside antibiotics and its unique structure is found in (S )-4-amino-2-hydroxyburyric acid substituted at C-1 of 2-deoxystreptamine. Recently, the key part of the butirosin biosynthetic gene cluster has been identified from Bacillus circulans SANK 72073, however the whole gene for the biosynthesis awaited for identification. In the present study, we undertook extended analysis of the butirosin biosynthetic gene cluster and found nine additional open reading flames (ORFs), btrQ, btrR1, btrR2, btrT, btrU, btrV, btrW, btrX and orf1 in the cluster. In addition, we constructed disruption mutants of btrR1 and btrP-V, and found that the btr genes (ca. 24 Kb) between btrR1 and btrP-V are at least required for the butirosin biosynthesis.

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“…[16] The biosynthetic pathway for ribostamycin was proposed based on the feeding of labelled precursors and the isolation of intermediates from blocked mutants of producer strains (Scheme 1). [17] The biosynthesis of 2 from d-glucose-6-phosphate (1) has been extensively characterized. [5,18,19] 2-DOS is thought to be converted to neamine (rings I and II) by the addition of the primary metabolite N-acetyl-d-glucosamine (GlcNAc) at C-4 by an as-yetuncharacterized glycosyltransferase to give N-acetylparoma-The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl:l-glutamate aminotransferase, respectively.…”

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confidence: 99%

Elaboration of Neosamine Rings in the Biosynthesis of Neomycin and Butirosin

et al. 2007

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The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl:L-glutamate aminotransferase, respectively. The joint activity of Neo-11 and Neo-18 is responsible for the conversion of paromamine to neamine in the biosynthetic pathway of neomycin through a mechanism of FAD-dependent dehydrogenation followed by a pyridoxal-5'-phosphate-mediated transamination. Neo-18 is also shown to catalyze deamination at C-6''' of neomycin, thus suggesting bifunctional roles of the two enzymes in the formation of both neosamine rings of neomycin. The product of the btrB gene, a homologue of neo-18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans, exhibits the same activity as Neo-18; this indicates that there is a similar reaction sequence in both butirosin and neomycin biosynthesis.

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Biosynthesis of butirosins. II. Biosynthetic pathway of butirosins elucidated from cosynthesis and feeding experiments.

Abstract: By cosynthetic studies, nine butirosin-non-producing blocked mutants of Bacillus circulans

Cited by 38 publications

References 22 publications

Biosynthetic genes for aminoglycoside antibiotics

Biosynthetic genes for aminoglycoside antibiotics

Extended Sequence and Functional Analysis of the Butirosin Biosynthetic Gene Cluster in Bacillus circulans SANK 72073

Elaboration of Neosamine Rings in the Biosynthesis of Neomycin and Butirosin

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