Streptomyces venezuelae, N. Sp., the Source of Chloromycetin

Ehrlich, John; Gottlieb, David; Burkholder, Paul R.; Anderson, Lucia E.; Pridham, T. G.

doi:10.1128/jb.56.4.467-477.1948

Cited by 87 publications

(27 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This bacterium produces chloramphenicol (chloromycetin), which served as the first broad-spectrum antibiotic used in clinical settings. 3 Due to its significant side effects, however, it has since been replaced with newer less toxic drugs in developed countries. In addition to chloramphenicol, S. venezuelae also produces methymycin, pikromycin, and other related macrolide-based antibacterial agents.…”

Section: Introductionmentioning

confidence: 99%

The structure of DesR from Streptomyces venezuelae, a β‐glucosidase involved in macrolide activation

2013

View full text Add to dashboard Cite

Antibiotics have, indeed, altered the course of human history as is evidenced by the increase in human life expectancy since the 1940s. Many of these natural compounds are produced by bacteria that, by necessity, must have efficient self-resistance mechanisms. The methymycin/pikromycin producing species Streptomyces venezuelae, for example, utilizes b-glucosylation of its macrolide products to neutralize their effects within the confines of the cell. Once released into the environment, these compounds are activated by the removal of the glucose moiety. In S. venezuelae, the enzyme responsible for removal of the sugar from the parent compound is encoded by the desR gene and referred to as DesR. It is a secreted enzyme containing 828 amino acid residues, and it is known to be a retaining glycosidase. Here, we describe the structure of the DesR/D-glucose complex determined to 1.4-Å resolution. The overall architecture of the enzyme can be envisioned in terms of three regions: a catalytic core and two auxiliary domains. The catalytic core harbors the binding platform for the glucose ligand. The first auxiliary domain adopts a ''PA14 fold,'' whereas the second auxiliary domain contains an immunoglobulin-like fold. Asp 273 and Glu 578 are in the proper orientation to function as the catalytic base and proton donor, respectively, required for catalysis. The overall fold of the core region places DesR into the GH3 glycoside hydrolase family of enzymes. Comparison of the DesR structure with the b-glucosidase from Kluyveromyces marxianus shows that their PA14 domains assume remarkably different orientations.

show abstract

Section: Introductionmentioning

confidence: 99%

The structure of DesR from Streptomyces venezuelae, a β‐glucosidase involved in macrolide activation

2013

View full text Add to dashboard Cite

show abstract

“…Remarks: Closely related to Nocardia corallina. 16. Nocardia rubropertincta (Hefferan) Waksman and Henrici.…”

Section: Gram-positivementioning

confidence: 99%

“…It is the hope of the authors that in spite of the above limitations, this guide will thus make available the rapidly accumulating information on the classification and characterization of the actinomycetes, a group of organisms that have now become famous because of their ability to produce a most interesting and valuable group of metabolic products, namely the antibiotics. 33, 148 coeliaca, 33, 135, 144, 153, 218 corallina, 33, 133, 134, 140, 141, 142, 144 cuniculi, 34, 151 32, 134, 144 paraffinae, 30, 33, 139 pelletieri, 34, 157 polychromogenes, 31,32,133,134 pretoriana, 32,137 pulmonalis, 33 13,20,21,22,72,189,191,195,203,209,221,227,229 Leben, Stessel and Keitt,16,96 lieskei,11,50 limosus,11,51 lipmanii, 16, 41, 93, 102, 192 h'sfen, 19, 118 loidensis, 18, 108, 110 longisporoflavus , 16,26,94 longispororuber , 17, 99 longisporus , 8, 9, 39…”

Section: In Retrospectmentioning

confidence: 99%

Guide to the Classification and Identification of the Actinomycetes and Their Antibiotics

Haley¹

1955

Medical Journal of Australia

View full text Add to dashboard Cite

Description of the Antibiotics of Actinomycetes Selected General References Index to Species of Actinomycetes 241 Index to Antibiotics of Actinomycetes vii PART I The Actinomycetes By Selman A. Waksman Classification of the Actinomycetes Classification of Actinomycetes According to Bergey According to the latest edition of Bergey's Manual, the order ACTINO-MYCETALES is divided into three families, Mycobacteriaceae, Actinomycetaceae, and Streptomycetaceae. The first family comprises the genus Mycobacterium, which is beyond the scope of this treatise. The second and third families comprise the true actinomycetes, with which this treatise is primarily concerned. The genera Nocardia and Actinomyces fall into the second family, and the genera Streptomyces and Micromonospora belong to the third. Another genus has recently been added, Thermoactinomyces, comprising largely certain thermophilic forms. Of the various species belonging to the five genera of true actinomycetes, those of the genus Actinomyces have not, so far, been found capable of producing antibiotics. Among the species belonging to the other four genera, those of the genus Streptomyces are by far the most important; hence a detailed consideration of the nature of this genus is justified. The Genus Streptomyces Species of Streptomyces produce a well-developed mycelium. The diameter of the hyphae seldom exceeds 1.0 p and is usually only 0.7-0.8 /z. The hyphae vary greatly in length. Some are long with limited branching; others are short and much branched. The vegetative mycelium does not form cross walls; it does not break up into rod-shaped and coccus-like bodies. The streptomycetes reproduce by means of conidia or by bits of mycelium. The spores or conidia are formed in special spore-bearing hyphae or sporophores which arise from the aerial mycelium, either monopodially or in the form of tufts or whorls. The sporulating hyphae are straight or CLASSIFICATION OF THE ACTINOMYCETES 6 curved. The curvatures range from mere waviness to the formation of perfect spirals, which may be compact, in the form of fists, or long and loose. The growth of streptomyces "colonies" on artificial media is smooth or lichnoid, hard and densely textured, raised, and adhering to the medium. The colony is usually covered completely or partially, in the form of spots or concentric rings, by aerial mycelium, which may be variously pigmented, depending on the species and on the composition of medium. In liquid media, especially in shaken cultures, growth of a streptomyces is usually in the form of flakes, which gradually fill the container, or in the form of spherical growths or puffballs. It is the former type of growth that is most desirable from the point of view of antibiotic production. Antagonistic properties: Usually none. Some strains produce actinomycetin. Some produce thiolutin or endomycin. Habitat: Universal occurrence in dust and soil. Remarks: Because of the universality of this species and the ease of its superficial identification, numerous strains with varying physiol...

show abstract

“…Chloramphenicol is an antibiotic which is produced by an actinomycete, Streptomyces venezuelae (Ehrlich et al, 1947(Ehrlich et al, , 1948Gottlieb et al, 1948). The structure of the molecule (D-(-) threo -2 -dichloracetamido -1 -pnitrophenyl-1,3-propanediol) is comparatively simple compared with that of most antibiotics (Rebstock et al, 1949).…”

mentioning

confidence: 99%