How many genes are required for the synthesis of chlortetracycline?

Ванек, З.; Cudlín, J.; Блумауерова, М.; Hošťálek, Z.

doi:10.1007/bf02884211

Cited by 42 publications

(12 citation statements)

References 15 publications

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“…It was proposed that 200-400 genes are involved in the biosynthesis of tetracycline and a cluster of genes was also postulated participating in final steps of tetracycline biosynthesis. It was also suggested that a similar theoretical approach could certainly be extended to secondary metabolites other than oligoketides and further improve our knowledge in the field which, in spite of its extraordinary importance in practical applications, remained only little elaborated in its theoretical aspects (Vaněk et al 1971).…”

Section: Tetracyclinesmentioning

confidence: 99%

“…In a stimulative hypothesis entitled BHow many genes are needed for the biosynthesis of chlortetracycline ( Vaněk et al 1971;Hošťálek and Vaněk 1985), the biosynthetic process leading to tetracyclines was divided into several parts of metabolic pathways, one part leading from glucose to pyruvate, another part of its transformation to acetyl-CoA and formation of a hypothetical tricyclic nonaketide, and the part of enzymatic reactions leading to the final product, i.e., chlortetracycline. This last part of biosynthesis was proposed to represent a chain of 11 enzymatic steps, compiled on the principles of logical chemical reactions.…”

Section: Tetracyclinesmentioning

confidence: 99%

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Biogenesis of antibiotics—viewing its history and glimpses of the future

et al. 2016

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This review aims at comparing some historical data with the current situation in the study of biogenesis of natural compounds, antibiotics in the first place. Biogenesis of tetracyclines and cycloheximide and related compounds serves as example. Examples of molecular biological and bioinformatics methods used in the study of antibiotic biogenesis are described both in terms of its historical aspects and the current knowledge.

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Section: Tetracyclinesmentioning

confidence: 99%

Section: Tetracyclinesmentioning

confidence: 99%

Biogenesis of antibiotics—viewing its history and glimpses of the future

et al. 2016

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“…However, the isolation of the blocked S. aureofaciens mutant by Ryan (73), producing 6-demethyl--CTC, confi rms that methylation at C6 is not obligatory as the earliest step in the modifi cation of the pretetramide. Hence, it is likely the most preferred route (30,74). The C6 methylation is probably followed by a double hydroxylation of ring A at C4/C12a by oxygenase pairs OxyL in OxyE, whereas OxyE is believed to be an ancillary monooxygenase for OxyL with a nonessential but important role in improving its catalytic effi ciency as a C4 hydroxylase (7 and 8 in Fig.…”

Section: Tailoring Reactions Of the Basic Tetracycline Backbonementioning

confidence: 99%

Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics

Petković

Lukežič²,

Šušković

2017

Food Technol. Biotechnol.

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SummaryNatural tetracycline (TC) antibiotics were the fi rst major class of therapeutics to earn the distinction of 'broad-spectrum antibiotics' and they have been used since the 1940s against a wide range of both Gram-positive and Gram-negative pathogens, mycoplasmas, intracellular chlamydiae, rickett siae and protozoan parasites. The second generation of semisynthetic tetracyclines, such as minocycline and doxycycline, with improved antimicrobial potency, were introduced during the 1960s. Despite emerging resistance to TCs erupting during the 1980s, it was not until 2006, more than four decades later, that a third--generation TC, named tigecycline, was launched. In addition, two TC analogues, omadacycline and eravacycline, developed via (semi)synthetic and fully synthetic routes, respectively, are at present under clinical evaluation. Interestingly, despite very productive early work on the isolation of a Streptomyces aureofaciens mutant strain that produced 6-demethyl-7-chlortetracycline, the key intermediate in the production of second-and third-generation TCs, biosynthetic approaches in TC development have not been productive for more than 50 years. Relatively slow and tedious molecular biology approaches for the genetic manipulation of TC-producing actinobacteria, as well as an insuffi cient understanding of the enzymatic mechanisms involved in TC biosynthesis have signifi cantly contributed to the low success of such biosynthetic engineering eff orts. However, new opportunities in TC drug development have arisen thanks to a signifi cant progress in the development of aff ordable and versatile biosynthetic engineering and synthetic biology approaches, and, importantly, to a much deeper understanding of TC biosynthesis, mostly gained over the last two decades.

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“…During these biosynthetic processes, coordinate reactions by biosynthetic enzymes were required for the complete formation of CTC, because a disorder of the coordinated reactions, usually caused by a mutation, resulted in the generation of at least nineteen CTCrelated shunt compounds. [1][2][3] Among these CTC-related compounds, only four compounds, tetracycline, CTC, 6-demethylchlortetracycline (6-DCT), and 6-demethyltetracycline (6-DMT), have antibacterial activity. These four compounds were characterized by the presence of a single bond at the 5a,11a-position, in contrast to other shunt products, which have a double bond at this position.…”

Section: Streptomyces Aureofaciensmentioning

confidence: 99%