Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds

Flatt, Patricia M.; Mahmud, Taifo

doi:10.1039/b603816f

Cited by 124 publications

(130 citation statements)

References 183 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…The gene for the aminoglycoside 3¢-phosphotransferase is typically found in or near the biosynthetic gene cluster as observed for the aminoglycosides neomycin, ribostamycin, streptomycin and gentamicin, among others. 21 The 3¢-hydroxy group of A-500359s is essential for translocase I inhibitory activity (unpublished data), thus consistent with ORF21 catalyzing the phosphorylation of the hexuronic acid moiety of A-500359s as a mechanism for self-resistance. An efficient transformation system in S. griseus SANK60196 has not yet been developed; thus, the functional analysis of orf21 was heterologously conducted in S. albus J1074 and E. coli DtolC.…”

Section: Functional Analysis Of Orf21supporting

confidence: 52%

Identification of the biosynthetic gene cluster of A-500359s in Streptomyces griseus SANK60196

et al. 2009

View full text Add to dashboard Cite

A-500359s, produced by Streptomyces griseus SANK60196, are inhibitors of bacterial phospho-N-acetylmuramyl-pentapeptide translocase. They are composed of three distinct moieties: a 5¢-carbamoyl uridine, an unsaturated hexuronic acid and an aminocaprolactam. Two contiguous cosmids covering a 65-kb region of DNA and encoding 38 open reading frames (ORFs) putatively involved in the biosynthesis of A-500359s were identified. Reverse transcriptase PCR showed that most of the 38 ORFs are highly expressed during A-500359s production, but mutants that do not produce A-500359s did not express these same ORFs. Furthermore, orf21, encoding a putative aminoglycoside 3¢-phosphotransferase, was heterologously expressed in Escherichia coli and Streptomyces albus, yielding strains having selective resistance against A-500359B, suggesting that ORF21 phosphorylates the unsaturated hexuronic acid as a mechanism of self-resistance to A-500359s. In total, the data suggest that the cloned region is involved in the resistance, regulation and biosynthesis of A-500359s.

show abstract

Section: Functional Analysis Of Orf21supporting

confidence: 52%

Identification of the biosynthetic gene cluster of A-500359s in Streptomyces griseus SANK60196

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Ninety-three percent of species harbor saccharide gene clusters, and in 33% of species, more than half of the predicted gene clusters encode saccharides. Cell-associated saccharides such as lipopolysaccharides (Park et al, 2009), capsular polysaccharides (Kadioglu et al, 2008), and polysaccharide A (Mazmanian et al, 2005;Mazmanian et al, 2008) are known to play key roles in microbe-host and microbe-microbe interactions, while diffusible saccharides have a range of biological activities, most notably antibacterial (Flatt and Mahmud, 2007;Weitnauer et al, 2001). The functions of many of the putative saccharide BGCs are still a mystery: 32%, including BGCs from entirely unexplored genera, are not closely related to any known gene cluster ( Figure S1E).…”

Section: Resultsmentioning

confidence: 99%

Galaxy masses

et al. 2014

View full text Add to dashboard Cite

“…The genes that encode the biosynthetic pathway for a small molecule are almost always clustered in the genome of their microbial producer (14,15), which undoubtedly reflects their evolutionary history through horizontal transmission (16). Because identifying one gene means the others are close by, cloning gene clusters for complete biosynthetic pathways is now straightforward and commonplace (17,18).…”

mentioning

confidence: 99%

The evolution of gene collectives: How natural selection drives chemical innovation

Fischbach

Walsh

Clardy

2008

Proc. Natl. Acad. Sci. U.S.A.

250

227

View full text Add to dashboard Cite

DNA sequencing has become central to the study of evolution. Comparing the sequences of individual genes from a variety of organisms has revolutionized our understanding of how single genes evolve, but the challenge of analyzing polygenic phenotypes has complicated efforts to study how genes evolve when they are part of a group that functions collectively. We suggest that biosynthetic gene clusters from microbes are ideal candidates for the evolutionary study of gene collectives; these selfish genetic elements evolve rapidly, they usually comprise a complete pathway, and they have a phenotype—a small molecule—that is easy to identify and assay. Because these elements are transferred horizontally as well as vertically, they also provide an opportunity to study the effects of horizontal transmission on gene evolution. We discuss known examples to begin addressing two fundamental questions about the evolution of biosynthetic gene clusters: How do they propagate by horizontal transfer? How do they change to create new molecules?

show abstract

Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds

Abstract: This review covers the biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds, particularly from the molecular genetic perspectives. 195 references are cited.

Cited by 124 publications

References 183 publications

Identification of the biosynthetic gene cluster of A-500359s in Streptomyces griseus SANK60196

Identification of the biosynthetic gene cluster of A-500359s in Streptomyces griseus SANK60196

Galaxy masses

The evolution of gene collectives: How natural selection drives chemical innovation

Contact Info

Product

Resources

About