Methodology for the rapid separation of gentamicin components and regiospecific synthesis of gentamicin conjugates

Grote, Jonathan; Himmelsbach, Richard J.; Johnson, Don

doi:10.1016/j.tetlet.2012.09.113

Cited by 11 publications

(11 citation statements)

References 10 publications

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“…Encouragingly, individual components of the gentamicin mixture may have lower toxicity ( 6 , 7 ). Individual components of gentamicin C can already be separated after manual chemical derivatization ( 8 ), but achieving this by low-cost direct fermentation would significantly advance interest in single components both as starting material for semisynthesis to novel gentamicins and for testing as therapeutics in their own right.…”

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confidence: 99%

Methyltransferases of gentamicin biosynthesis

Guo

Reva

et al. 2018

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

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SignificanceAminoglycosides remain a vital clinical asset. Gentamicin C complex in particular is remarkably potent in treating systemic Gram-negative infections, and semisynthetic gentamicins that combat pathogen resistance or show reduced toxicity remain attractive goals. We report here the roles of clustered genes and enzymes that define a methylation network in gentamicin biosynthesis and also identify a remote gene on the chromosome encoding the essential methyltransferase GenL, which is decisive for the proportions of the five major components present in the gentamicin C complex. This is an important step toward engineered fermentation to produce single components as valuable starting materials for semisynthesis of next-generation aminoglycoside antibiotics.

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confidence: 99%

Methyltransferases of gentamicin biosynthesis

Guo

Reva

et al. 2018

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

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“…As gentamicin is a complex consisting of several minor and three major components, the proportions of these components can vary depending on the fermentation process, and some of the impurities can be also toxic [311,324]. Therefore, pharmaceutical industries are usually earger to develop more powerful methods of separation.…”

Section: Bioprocess Development and Biotransformationmentioning

confidence: 99%

“…Therefore, pharmaceutical industries are usually earger to develop more powerful methods of separation. In 2012, Grote et al [324] described a method for synthesis of a single conjugate of gentamicin. They found that the reaction of the gentamicin complex with excess benzyl chloroformate provided a mixture of the amine protected components which can be separable by preparative HPLC using UV detection, which give opportunity to get a single gentamicin conjugate.…”

Section: Bioprocess Development and Biotransformationmentioning

confidence: 99%

Recent progress on the development of antibiotics from the genus Micromonospora

Boumehira

El‐Enshasy

Hacène

et al. 2016

Biotechnol Bioproc E

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The emergence of large number of antimicrobial-resistant organisms has given alarming magnitude. Nature is historically the source of drugs, and microorganisms have provided a significant number of antibiotic compounds, which are used every day in the treatment of many infectious diseases. However, the introduction to the pharmaceutical market of new therapeutic molecules has largely decreased during the last two decades. In this review, antibiotics from the genus Micromonospora are recognized as potential biofactory for new antibiotic production. The Micromonospora has been deeply studied and more than 100 antibiotics isolated from different Micromonospora strains. In addition, comprehensive information about the recent development in the field of analytical, biological and bioinformatics screening tools, which recently used in the discovery of new therapeutic compounds, are provided. It is widely believed that reviving old antibiotics produced by Micromonospora is possible and the study of this genus is still interesting for novel bioactive molecules discovery.

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“…[4] The fluorescent conjugate of gentamicin and Texas Red ( 1 -GT, Fig. 2) has been of great utility in the study of non-endocytotic aminoglycoside uptake and intracellular localization.…”

Section: Introductionmentioning

confidence: 99%