The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase.

@article{Fan2008TheNB,
  title={The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase.},
  author={Qingzhi Fan and Fanglu Huang and Peter F. Leadlay and Jonathan B. Spencer},
  journal={Organic \& biomolecular chemistry},
  year={2008},
  volume={6 18},
  pages={
          3306-14
        }
}
An efficient protocol has been developed for the genetic manipulation of Streptomyces fradiae NCIMB 8233, which produces the 2-deoxystreptamine (2-DOS)-containing aminoglycoside antibiotic neomycin. This has allowed the in vivo analysis of the respective roles of the glycosyltransferases Neo8 and Neo15, and of the deacetylase Neo16 in neomycin biosynthesis. Specific deletion of each of the neo8, neo15 and neo16 genes confirmed that they are all essential for neomycin biosynthesis. The pattern… Expand
Biosynthesis of Ribostamycin Derivatives by Reconstitution and Heterologous Expression of Required Gene Sets
TLDR
The present in vivo modification of ribostamycin could be useful for the production of hybrid compounds to defend against bacterial resistance to aminoglycosides. Expand
Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation.
TLDR
It is discovered that the kanamycin biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Expand
N-Deacetylation in Lincosamide Biosynthesis Is Catalyzed by a TldD/PmbA Family Protein.
TLDR
This work elucidated the N-deacetylation of the mycothiol-derived N-acetyl-l-cysteine residue of a lincosamide intermediate, which is comprised of an amino acid and an aminooctose connected via an amide bond, and presented a sequence similarity network of TldD/PmbA proteins, which suggests that the l incosamide N- deacetylases are unique among these widely distributed proteins. Expand
Heterologous production of paromamine in Streptomyces lividans TK24 using kanamycin biosynthetic genes from Streptomyces kanamyceticus ATCC12853
TLDR
The production of paromamine in a heterologous host for the first time is reported and will evoke to explore complete biosynthetic pathways of kanamycin and related aminoglycoside antibiotics. Expand
Delineating the Biosynthesis of Gentamicin X2, the Common Precursor of the Gentamicin C Antibiotic Complex
TLDR
New insights are reported into the four enzyme-catalyzed steps that lead from the first-formed pseudotrisaccharide gentamicin A2 to Gentamicin X2, the last common intermediate for all components of the C complex. Expand
Specificity and Promiscuity at the Branch Point in Gentamicin Biosynthesis
TLDR
Gentamicin C complex is a mixture of aminoglycoside antibiotics used to treat severe Gram-negative bacterial infections and key features of the late-stage biosynthesis of gentamicins are reported. Expand
A putative de-N-acetylase of the PIG-L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa.
TLDR
DnpA (de-N-acetylase involved in persistence) is presented as a new gene involved in noninherited fluoroquinolone tolerance in P. aeruginosa persistence and site-directed mutagenesis suggests that this enzymatic activity is essential for DnpA-mediated persistence. Expand
Heterologous expression of the kanamycin biosynthetic gene cluster (pSKC2) in Streptomyces venezuelae YJ003
TLDR
The pSKC2 cosmid, which has 32 kb and 28 open-reading frames, was isolated from Streptomyces kanamyceticus ATCC12853 as the gene cluster of kanamycin and showed the advantage of fast growth, good efficiency of the transformation host, and rapid production of the aminoglycosides antibiotic. Expand
Biosynthetic enzymes for the aminoglycosides butirosin and neomycin.
TLDR
The enzymatic reactions in the biosynthesis of butirosin and neomycin are reviewed step by step to shed light on the complex biosynthetic pathways for other related structurally diverse aminoglycoside antibiotics. Expand
2-Deoxystreptamine-containing aminoglycoside antibiotics: recent advances in the characterization and manipulation of their biosynthetic pathways.
TLDR
This work focuses on recent advances in the characterization of 2-deoxystreptamine-containing aminoglycosides and their biosynthetic enzymes and pathway as well as some chemo-enzymatic and metabolic engineering approaches for the biological production of natural, semi-synthetic, and novel aminglycosides. Expand
...
1
2
...

References

SHOWING 1-10 OF 35 REFERENCES
The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: characterisation of an aminotransferase involved in the formation of 2-deoxystreptamine.
TLDR
Three genes unique to the neo and btr clusters have been revealed by comparison of the neo cluster to btr, gnt, tbm and kan clusters, which suggests that these three genes may be involved in the transfer of a ribose moiety to the DOS ring during the antibiotic biosynthesis. Expand
Involvement of Two Distinct N‐Acetylglucosaminyltransferases and a Dual‐Function Deacetylase in Neomycin Biosynthesis
TLDR
Neomycin is one of the clinically important 2-deoxystreptamine (DOS)-containing aminoglycoside antibiotics, which specifically interact with bacterial rRNA and inhibit protein synthesis, and neoD was presumed to catalyze N-acetylglucosaminylation of DOS. Expand
Biosynthesis of 2-Deoxystreptamine by Three Crucial Enzymes in Streptomyces fradiae NBRC 12773
TLDR
Since NeoB (Neo6) was also reported to be L-glutamine:2-deoxy-scyllo-inosose aminotransferase, all the enzymes in the DOS biosynthesis were characterized for the first time. Expand
A new family of glucose-1-phosphate/glucosamine-1-phosphate nucleotidylyltransferase in the biosynthetic pathways for antibiotics.
TLDR
It appears therefore that gene clusters for antibiotic biosynthesis provide their own nucleotidylyltransferases, and the BtrD homologues are among the secondary metabolism specific enzymes. Expand
'Streptomyces nanchangensis', a producer of the insecticidal polyether antibiotic nanchangmycin and the antiparasitic macrolide meilingmycin, contains multiple polyketide gene clusters.
TLDR
P pHZ1358 was shown to be generally useful for generating mutant strains by gene disruption and replacement in NS3226 as well as in several other Streptomyces strains. Expand
Construction of new vectors for high-level expression in actinomycetes.
TLDR
PCJR24-mediated recombination was used to place the entire gene set for the erythromycin-producing polyketide synthase under the control of the actI promoter, and provided the means for rational strain improvement of antibiotic-producing actinomycetes. Expand
Unique O-ribosylation in the biosynthesis of butirosin.
TLDR
Functional analysis of the recombinantly expressed proteins revealed that both BtrL and BtrP were responsible for the ribosylation of neamine, using 5-phosphoribosyl-1-diphosphate (PRPP) as the ribo-ribosyl donor. Expand
Organization of the biosynthetic gene cluster in Streptomyces sp. DSM 4137 for the novel neuroprotectant polyketide meridamycin.
TLDR
The characterization of theMeridamycin biosynthetic locus in this readily manipulated streptomycete species opens the way to the engineering of new, altered meridamycins of potential therapeutic importance. Expand
Biochemistry of the Initial Steps of Mycothiol Biosynthesis*
TLDR
The biochemical pathway of mycothiol biosynthesis is now fully elucidated and the presence of a myo-inositol transporter and a kinase that generates 1l-myo- inositol 1-phosphate is demonstrated. Expand
Overexpression and Characterization of the Chromosomal Aminoglycoside 2′-N-Acetyltransferase ofProvidencia stuartii
TLDR
Comparison of the kinetic parameters obtained with the different aminoglycosides indicated that their hexopyranosyl residues provided the most important binding sites for AAC(2′)-Ia activity, while the enzyme exhibits greater tolerance further from these sites. Expand
...
1
2
3
4
...