Jadomycin, a novel 8H-benz[b]oxazolo[3,2-f]phenanthridine antibiotic from from streptomyces venezuelae ISP5230.

Ayer, Stephen W.; McInnes, A. G.; Thibault, Pierre; Walter, John A.; Doull, James A.; Parnell, Tracy; Vining, L. C.

doi:10.1016/0040-4039(91)80152-v

Cited by 77 publications

(62 citation statements)

References 5 publications

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“…Post-PKS aromatization is a common phenomenon in angucycline and other aromatic polyketide biosynthetic pathways, e.g. in kinamycin (9) and landomycin biosyntheses (34 -37). The high similarities between the oxygenase enzymes involved in these biosyntheses (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…One unique feature of the jadomycin family is its nitrogencontaining pentacyclic benz [b]oxazolophenanthridine ring, formed via a hitherto uncharacterized oxidative cleavage between C-5 and C-6 of ring B in an angucyclic polyketide intermediate. The phenanthridine ring system is plausibly derived by condensation of an amino acid with the postulated acid/ aldehyde intermediate (5), formed during angucyclic ring opening (7,9). Strengthening this possibility is the formation of jadomycin analogues when different amino acids are supplied as precursors (10,11).…”

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confidence: 99%

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Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase

Chen

Wang

Greenwell

et al. 2005

Journal of Biological Chemistry

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A novel angucycline metabolite, 2,3-dehydro-UWM6, was identified in a jadH mutant of Streptomyces venezuelae ISP5230. Both UWM6 and 2,3-dehydro-UWM6 could be converted to jadomycin A or B by a ketosynthase ␣ (jadA) mutant of S. venezuelae. These angucycline intermediates were also converted to jadomycin A by transformant of the heterologous host Streptomyces lividans expressing the jadFGH oxygenases in vivo and by its cell-free extracts in vitro; thus the three gene products JadFGH are implicated in catalysis of the postpolyketide synthase biosynthetic reactions converting UWM6 to jadomycin aglycone. Genetic and biochemical analyses indicate that JadH possesses dehydrase activity, not previously associated with polyketide-modifying oxygenase. Since the formation of aromatic polyketides often requires multiple dehydration steps, bifunctionality of oxygenases modifying aromatic polyketides may be a general phenomenon.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase

Chen

Wang

Greenwell

et al. 2005

Journal of Biological Chemistry

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“…[1][2][3][4] Here we deal with jadomycin derivatives, which form a series of angucycline-derived molecules with a unique pentacyclic benz [b]oxazolophenanthridine skeleton, 5,6 produced by Streptomyces venezuelae ISP5230 under stress conditions, such as phage infection, heat and ethanol shock. 7 Jadomycin provides a model system to study secondary metabolism in streptomycetes, with unique biosynthetic and regulatory features.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells

et al. 2012

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The jadomycins are a unique family of angucycline-derived antibiotics with interesting cytotoxic activities. In this work, six new jadomycin derivatives were produced in vivo by providing non-natural amino acids in fermentation media. They were further purified and identified by MS and NMR analyses. The cytotoxicities of these derivatives were evaluated against tumor cell lines MCF-7 and HCT116, as well as the normal human microvascular epithelial cells. The derivatives with alkyl side chains showed similar levels of cytotoxicity as jadomycin B and other known derivatives with nonpolar side chains, with IC 50 ranging from 1.3 to 10 lM; but the activities are not selective as these compounds also showed similar levels of cytotoxicity toward the normal human microvascular epithelial cells in the same concentration range. For the first time, derivatives with amino side chains (jadomycin Orn and K) were prepared and evaluated. Significantly, jadomycin Orn showed differential activity against normal and tumor cell lines. This result points to a new direction to modify jadomycin structure. The insights on the structure-activity relationship of jadomycins will guide further efforts to generate new and improved jadomycin derivatives against tumor cells.

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“…The jadomycins are a family of antibiotics discovered serendipitously while exploring culture conditions for the production of chloramphenicol. 3 Jadomycin A 3 and subsequently the glycosylated analogue, jadomycin B, 4 were discovered when the bacteria was subjected to heat, phage, or ethanol shock. Since this initial discovery, the jadomycin scaffold has been shown to be amenable to alteration through the incorporation of both proteinogenic and nonproteinogenic amino acids.…”

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confidence: 99%

“…1 Analysis of these clusters and their natural products may result in unique structural diversity or bioactivity. The soil bacteria Streptomyces venezuelae ISP5230 (ATCC 10712) has been shown to contain over 30 secondary metabolite gene clusters, 1 where only those of chloramphenicol 2 and jadomycin 3 have been studied. The jadomycins are a family of antibiotics discovered serendipitously while exploring culture conditions for the production of chloramphenicol.…”

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confidence: 99%

Isolation and Synthetic Diversification of Jadomycin 4-Amino-l-phenylalanine

Martinez-Farina¹,

Robertson²,

Yin

et al. 2015

J. Nat. Prod.

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Jadomycin, a novel 8H-benz[b]oxazolo[3,2-f]phenanthridine antibiotic from from streptomyces venezuelae ISP5230.

Cited by 77 publications

References 5 publications

Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase

Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase

Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells

Isolation and Synthetic Diversification of Jadomycin 4-Amino-l-phenylalanine

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