Biosynthesis of clavam metabolites

Jensen, Susan E.

doi:10.1007/s10295-012-1191-0

Cited by 36 publications

(53 citation statements)

References 78 publications

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“…Unusually, the TTA-containing CSR gene ccaR for clavulanic acid/cephamycin C biosynthesis in S. clavuligerus is fully expressed in a bldA mutant (160,161). This is thought to indicate a context effect on the extent to which UUA codons are translatable in a bldA mutant, with UUA codons followed by G or A being more likely to be mistranslated in frame (160,161).…”

Section: A Special Regulatory Role For the Rare Leucine Codon Uua In mentioning

confidence: 99%

“…This is thought to indicate a context effect on the extent to which UUA codons are translatable in a bldA mutant, with UUA codons followed by G or A being more likely to be mistranslated in frame (160,161). Further analysis of this hypothesis is needed in order that the effects of TTA codons in antibiotic gene clusters can be reliably predicted.…”

Section: A Special Regulatory Role For the Rare Leucine Codon Uua In mentioning

confidence: 99%

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Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

610

536

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SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

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Section: A Special Regulatory Role For the Rare Leucine Codon Uua In mentioning

confidence: 99%

Section: A Special Regulatory Role For the Rare Leucine Codon Uua In mentioning

confidence: 99%

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

610

536

View full text Add to dashboard Cite

show abstract

“…In an interesting counterpoint to the bldA story, the TTA codon in ccrA, the CSR gene controlling cephamycin C and clavulanic acid biosynthesis in S. clavuligerus , does not make the production of CcrA bldA -dependent 125 . It has now turned out that many, but not all, TTA-containing genes in S. clavuligerus display the same anomaly 126 .…”

Section: A High-resolution Global Survey Of Gene Expression In S Coementioning

confidence: 99%

Recent advances in understanding Streptomyces

2016

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About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome immunoprecipitation sequencing (ChIP-seq) analysis and other methods based on “next-generation sequencing” has been the finding that 21% of Streptomyces mRNA species lack leader sequences and conventional ribosome binding sites. Further technical advances now emerging should lead to continued acceleration of knowledge, and more effective exploitation, of these astonishing and critically important organisms.

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“…O ácido clavulânico apresenta uma pequena atividade antibiótica, mas potente atividade inibitória das β-lactamases. Portanto, o ácido clavulânico comercializado é associado a amoxicilina (JENSEN, 2012). O ácido clavulânico é um metabólito secundário produzido pelo Streptomyces clavuligerus.…”

Section: Introductionunclassified

Determinação Do Ph E Temperatura Ótimos Para a Produtividade Do Ácido Clavulânico Utilizando O Streptomyces Clavuligerus Atcc 27064

Pinelli¹,

Dias²

2017

MUNDI ETG

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Determinação do pH e temperatura ótimos para a produtividade do ácido clavulânico utilizando o Streptomyces clavuligerus ATCC 27064Determination of pH and temperature optimum on the productivity of clavulanic acid using Streptomyces clavuligerus ATCC 27064Juliana Junqueira Pinelli 1 Sandra de Cássia Dias 2 Resumo: O ácido clavulânico (AC) é um metabólito secundário produzido pela bactéria GramPositiva Streptomyces clavuligerus. É um composto de suma importância, principalmente para a indústria farmacêutica, pois possui ação antibacteriana. É utilizado em associação com outros antibióticos, como a amoxicilina. Sua produção ocorre por via fermentativa. O pH e a temperatura do meio são parâmetros relevantes que podem comprometer a produção deste metabólito. O presente trabalho teve como objetivo avaliar a influência da temperatura e do pH na produção de ácido clavulânico a partir de Streptomyces clavuligerus ATCC 27064. Para isso, um número mínimo de experimentos foi desenhado com diferentes valores de pH e temperatura utilizando o planejamento experimental estatístico, delineamento composto central rotacional, DCCR, tendo como variáveis pH e temperatura e como resposta a produtividade do ácido clavulânico. Amostras foram retiradas a cada 12 horas e a produção de ácido clavulânico determinada por método espectrofotométrico. O cultivo realizado em pH 6,7 e temperatura 27ºC apresentou maior produtividade do ácido clavulânico. Palavras-chave:Delineamento composto central rotacional. Antibiótico. Metodologia de superfície de resposta. Bioprocessos Abstract: Clavulanic acid (CA) is a secondary metabolite produced by the Gram-Positive bacteria Streptomyces clavuligerus. It is a compound of great importance, mainly for the pharmaceutical industry, because it has antibacterial activity. It is used in combination with other antibiotics such as amoxicillin. Its production occurs by fermentation. The pH and temperature of the medium are relevant parameters that can compromise the production of this metabolite. The aim of this study was to evaluate the temperature and pH influence on the clavulanic acid productivity by Streptomyces clavuligerus ATCC 27064. For this, a minimum number of experiments were designed with different values of pH and temperature using statistical experimental design, central composite rotational design (CCRD) having as variables pH and temperature and as response the clavulanic acid productivity. Samples were collected every 12 hours and the clavulanic acid production was determined by spectrophotometric method. The cultivation carried out at pH 6.7 and temperature 27ºC showed the highest clavulanic acid productivity.

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Biosynthesis of clavam metabolites

Cited by 36 publications

References 78 publications

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Recent advances in understanding Streptomyces

Determinação Do Ph E Temperatura Ótimos Para a Produtividade Do Ácido Clavulânico Utilizando O Streptomyces Clavuligerus Atcc 27064

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