The biosynthesis of AR-5 (mycinamicins) antibiotics.

Puar, Mohindar S.; Lee, B. K.; Munayyer, H.; Brambilla, Raymond; Waitz, J. A.

doi:10.7164/antibiotics.34.619

Cited by 10 publications

(7 citation statements)

References 6 publications

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“…Puar et al[2] reported that three molecules of acetate and five molecules of propionate were used in the biosynthesis of AR‐5 (mycinamicin). Almost all molecules of acetate and propionate used in macrolide biosynthesis appear to be derived from malonyl‐CoA and methylmalonyl‐CoA, respectively [12,14].…”

Section: Resultsmentioning

confidence: 99%

“…1), is produced by Micromonospora griseorubida , and has strong antibacterial activity against Gram‐positive bacteria[1]. Details of the biosynthetic pathway for mycinamicins have been studied with organic chemical and fermentation techniques [2–4], but only two genes for mycinamicin II biosynthesis have been cloned and identified: mycF encoding mycinamicin III O ‐methyltransferase, and mycG encoding a P450‐like protein responsible for both the hydroxylation and epoxidization of the lactone ring of mycinamicin [5,6]. Two mycinamicin II resistance genes, myrA and myrB , were also isolated from M. griseorubida [7], and mycG , mycF and a putative PKS open reading frame (ORF) were located downstream of myrB [8].…”

Section: Introductionmentioning

confidence: 99%

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Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin inMicromonospora griseorubida

Anzai

Saito

Tanaka

et al. 2003

FEMS Microbiology Letters

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Mycinamicin, composed of a branched lactone and two sugars, desosamine and mycinose, at the C-5 and C-21 positions, is a 16-membered macrolide antibiotic produced by Micromonospora griseorubida A11725, which shows strong antimicrobial activity against Gram-positive bacteria. The nucleotide sequence (62 kb) of the mycinamicin biosynthetic gene cluster, in which there were 22 open reading frames (ORFs), was completely determined. All of the products from the 22 ORFs are responsible for the biosynthesis of mycinamicin II and self-protection against the compounds synthesized. Central to the cluster is a polyketide synthase locus (mycA), which encodes a seven-module system comprised of five multifunctional proteins. Immediately downstream of mycA, there is a set of genes for desosamine biosynthesis (mydA-G and mycB). Moreover, mydH, whose product is responsible for the biosynthesis of mycinose, lies between mydA and B. On the other hand, eight ORFs were detected upstream of the mycinamicin PKS gene. The myrB, mycG, and mycF genes had already been characterized by Inouye et al. The other five ORFs (mycCI, mycCII, mydI, mycE, and mycD) lie between mycA1 and mycF, and these five genes and mycF are responsible for the biosynthesis of mycinose. In the PKS gene, four regions of KS and AT domains in modules 1, 4, 5, and 6 indicated that it does not show the high GC content typical for Streptomyces genes, nor the unusual frame plot patterns for Streptomyces genes. Methylmalonyl-CoA was used as substrate in the functional units of those four modules. The relationship between the substrate and the unusual frame plot pattern of the KS and AT domains was observed in the other PKS genes, and it is suggested that the KS-AT original region was horizontally transferred into the PKS genes on the chromosomal DNA of several actinomycetes strains.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin inMicromonospora griseorubida

Anzai

Saito

Tanaka

et al. 2003

FEMS Microbiology Letters

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“…Puar et al [2] reported that three molecules of acetate and ¢ve molecules of propionate were used in the biosyn- [12]. Phylogenetic trees were constructed by the neighbor-joining method using the CLUSTAL X program.…”

Section: Myca Has Regions Of Unusual Coding Sequencementioning

confidence: 99%

Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida

Anzai¹

2003

FEMS Microbiology Letters

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Mycinamicin, composed of a branched lactone and two sugars, desosamine and mycinose, at the C-5 and C-21 positions, is a 16-membered macrolide antibiotic produced by Micromonospora griseorubida A11725, which shows strong antimicrobial activity against Gram-positive bacteria. The nucleotide sequence (62 kb) of the mycinamicin biosynthetic gene cluster, in which there were 22 open reading frames (ORFs), was completely determined. All of the products from the 22 ORFs are responsible for the biosynthesis of mycinamicin II and self-protection against the compounds synthesized. Central to the cluster is a polyketide synthase locus (mycA), which encodes a seven-module system comprised of five multifunctional proteins. Immediately downstream of mycA, there is a set of genes for desosamine biosynthesis (mydA^G and mycB). Moreover, mydH, whose product is responsible for the biosynthesis of mycinose, lies between mydA and B. On the other hand, eight ORFs were detected upstream of the mycinamicin PKS gene. The myrB, mycG, and mycF genes had already been characterized by Inouye et al. The other five ORFs (mycCI, mycCII, mydI, mycE, and mycD) lie between mycA1 and mycF, and these five genes and mycF are responsible for the biosynthesis of mycinose. In the PKS gene, four regions of KS and AT domains in modules 1, 4, 5, and 6 indicated that it does not show the high GC content typical for Streptomyces genes, nor the unusual frame plot patterns for Streptomyces genes. Methylmalonyl-CoA was used as substrate in the functional units of those four modules. The relationship between the substrate and the unusual frame plot pattern of the KS and AT domains was observed in the other PKS genes, and it is suggested that the KS-AT original region was horizontally transferred into the PKS genes on the chromosomal DNA of several actinomycetes strains. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.

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“…Thus, rosaramicin (7) on treatment with thioacetic S-acid (2 equiv.) at 25 "C for 21 h, afforded a single diastereoisomer, namely ( 1 1 R)-11 -acetylthio-lO,l 1-dihydrorosaramicin (49) in Me ( 7 )…”

mentioning

confidence: 99%

“…In order to study the shielding effects of the 1 1 -substituent on neighbouring groups, we felt that it would be advantageous to prepare the 1 l-phenylthio derivatives in view of the larger anisotropic effect of the phenyl ring. The desired 1 l-phenylthio derivatives were prepared by the direct Michael addition of thiophenol to rosaramicin (7) to give the 11 Rand 1 1 -S-phenylthio adducts (50) and (51) respectively; to deepoxyrosaramicin (15) to give the l l Rand 1 l-S-phenylthio adducts (58) and (59) respectively; and to desmycosin (32)…”

mentioning

confidence: 99%

Novel semisynthetic oxo and alkyl macrolide antibacterials and related derivatives

Fishman¹,

Mallams²,

Puar³

et al. 1987

J. Chem. Soc., Perkin Trans. 1

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The biosynthesis of AR-5 (mycinamicins) antibiotics.

Cited by 10 publications

References 6 publications

Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin inMicromonospora griseorubida

Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin inMicromonospora griseorubida

Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida

Novel semisynthetic oxo and alkyl macrolide antibacterials and related derivatives

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