Total synthesis of antibiotic indolmycin and its stereoisomers

Preobrazhenskaya, M. N.; Balashova, E. G.; Turchin, K. F.; Padeiskaya, E. N.; Uvarova, N.V.; Pershin, G. N.; Суворов, Н. Н.

doi:10.1016/s0040-4020(01)96345-8

Cited by 45 publications

(11 citation statements)

References 4 publications

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“…However, this indolmycin concentration, is higher than the minimum inhibitory concentration values of previously reported indolmycin-sensitive bacteria, for example: Pseudomonas aeruginosa (31-250 g/ml, Ref. 33), Mycobacterium tuberculosis (6 -16 g/ml, Ref. 33), and S. aureus Oxford (0.125 g/ml, Ref.…”

Section: Resultsmentioning

confidence: 54%

Indolmycin Resistance of Streptomyces coelicolor A3(2) by Induced Expression of One of Its Two Tryptophanyl-tRNA Synthetases

Kitabatake¹,

Ali²,

Demain³

et al. 2002

Journal of Biological Chemistry

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Aminoacyl-tRNA synthetases, a family of enzymes essential for protein synthesis, are promising targets of antimicrobials. Indolmycin, a secondary metabolite of Streptomyces griseus and a selective inhibitor of prokaryotic tryptophanyl-tRNA synthetase (TrpRS), was used to explore the mechanism of inhibition and to explain the resistance of a naturally occurring strain. Streptomyces coelicolor A3(2), an indolmycin-resistant strain, contains two trpS genes encoding distinct TrpRS enzymes. We show that TrpRS1 is indolmycin-resistant in vitro and in vivo, whereas TrpRS2 is sensitive. The lysine (position 9) in the enzyme tryptophan binding site is essential for making TrpRS1 indolmycin-resistant. Replacement of lysine 9 by glutamine, which at this position is conserved in most bacterial TrpRS proteins, abolished the ability of the mutant trpS gene to confer indolmycin resistance in vivo. Molecular modeling suggests that lysine 9 sterically hinders indolmycin binding to the enzyme. Tryptophan recognition (assessed by k cat / K M ) by TrpRS1 is 4-fold lower than that of TrpRS2. Examination of the mRNA for the two enzymes revealed that only TrpRS2 mRNA is constitutively expressed, whereas mRNA for the indolmycin-resistant TrpRS1 enzyme is induced when the cells are exposed to indolmycin.

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Section: Resultsmentioning

confidence: 54%

Indolmycin Resistance of Streptomyces coelicolor A3(2) by Induced Expression of One of Its Two Tryptophanyl-tRNA Synthetases

Kitabatake¹,

Ali²,

Demain³

et al. 2002

Journal of Biological Chemistry

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“…Compound 5 itself has been a focus of total synthetic efforts toward 1, as it is the key chiral precursor. 14,15,[22][23][24][25][26] Since production of 5 was much higher than that of 1 from E. coli I1234670P5, we pursued a semi-synthetic method of obtaining 1 using our biosynthetic platform to access 5, combined with a three-step chemical transformation (Fig. 2b).…”

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confidence: 99%

An engineered biosynthetic–synthetic platform for production of halogenated indolmycin antibiotics

Hoffarth

Kong

et al. 2021

Chem. Sci.

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“…Smears of fresh isolates were picked on slides and heat fixed and examined microscopically and by the routine bacteriological methods including: subculture in selective media, biochemical tests: indole test, 13 oxidase test, 14 catalase test, 15 gelatin hydrolysis, 16 Voges-Proskauer test, 17 methyl red test, 18 carbohydrate fermentation test, 19 API 20 NE and VITEK 2 system.…”

Section: Identificationmentioning

confidence: 99%

Detection of Burkholderia cepacia in pharmaceutical products

Fahmy¹,

Saleh²,

Khalil³

2020

IJMR

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Burkholderia cepacia complex (BCC) have recently received a reasonable attention as one of the major risks in susceptible pharmaceutical products. This microorganism can easily spread and cause severe contamination especially to the water stations for pharmaceutical companies. It rapidly grow within the product and cause cystic fibrosis and septicemia in humans. Aim: The traceability of the sources of contamination of pharmaceutical non-sterile aqueous preserved products and how to control it during the manufacturing operations as it is concern with the public health. Materials and Methods: The samples collected for the analysis were taken from different sources provided from the pharmaceutical company such as: aqueous finished products, filling machines, preparation tanks and water stations, identified by API 20NE, Vitek 2 compact system and 16S rRNA. Results: From 213 different samples of finished product, 22 bacterial isolates had been identified as Burkholderia cepacia group. Raw materials and primary packaging materials did not result in any bacterial isolates while the machine surfaces and preparation tanks were contaminated. From 384 pharmaceutical water samples, 35 isolates were identified as B.cepacia. Conclusion:Our study suggests that the chlorine treatment and hydrogen peroxide have a significant effect on B.cepacia in water disinfection.

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Total synthesis of antibiotic indolmycin and its stereoisomers

Cited by 45 publications

References 4 publications

Indolmycin Resistance of Streptomyces coelicolor A3(2) by Induced Expression of One of Its Two Tryptophanyl-tRNA Synthetases

Indolmycin Resistance of Streptomyces coelicolor A3(2) by Induced Expression of One of Its Two Tryptophanyl-tRNA Synthetases

An engineered biosynthetic–synthetic platform for production of halogenated indolmycin antibiotics

Detection of Burkholderia cepacia in pharmaceutical products

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