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Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.

Gomes ES, Schuch V, de Macedo Lemos EG - Braz. J. Microbiol. (2014)

Bottom Line: However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens.Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways.In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Tecnologia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus de Jaboticabal, Jaboticabal, SP, Brazil.

ABSTRACT
The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the "goose that laid the golden egg," the potential of this wealth is still inexorable: simply adjust the focus from "micro" to "nano", that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

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Related in: MedlinePlus

ORFs map of the sequenced metagenomic DNA insert for the clone B7B37. ORF1: PKSI biosynthesis gene cluster.
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f10-bmj-44-4-1007: ORFs map of the sequenced metagenomic DNA insert for the clone B7B37. ORF1: PKSI biosynthesis gene cluster.

Mentions: The metagenomic DNA insert obtained was 29,697 bp long. The mean GC content was 64%. Twenty-one ORFs were identified (Figure 10). The potential roles of the genes contained in the ORFs were determined by comparison with similar sequences present in the databases and functional domain analysis (Tables 1 and 2). All possible genes found in the sequenced region displayed typical characteristics of bacteria, and when subjected to database homology searches, each of the translated ORFs showed greater similarity to bacterial proteins.


Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.

Gomes ES, Schuch V, de Macedo Lemos EG - Braz. J. Microbiol. (2014)

ORFs map of the sequenced metagenomic DNA insert for the clone B7B37. ORF1: PKSI biosynthesis gene cluster.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3958165&req=5

f10-bmj-44-4-1007: ORFs map of the sequenced metagenomic DNA insert for the clone B7B37. ORF1: PKSI biosynthesis gene cluster.
Mentions: The metagenomic DNA insert obtained was 29,697 bp long. The mean GC content was 64%. Twenty-one ORFs were identified (Figure 10). The potential roles of the genes contained in the ORFs were determined by comparison with similar sequences present in the databases and functional domain analysis (Tables 1 and 2). All possible genes found in the sequenced region displayed typical characteristics of bacteria, and when subjected to database homology searches, each of the translated ORFs showed greater similarity to bacterial proteins.

Bottom Line: However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens.Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways.In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Tecnologia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus de Jaboticabal, Jaboticabal, SP, Brazil.

ABSTRACT
The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the "goose that laid the golden egg," the potential of this wealth is still inexorable: simply adjust the focus from "micro" to "nano", that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

Show MeSH
Related in: MedlinePlus