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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

Public and private initiative contributions to the discovery of new drugs in different countries for the period between 1998 and 2007. Reproduced from Nature Reviews Drug Discovery, November 2010, Vol. 9, Pages 867–882 with permission of Nature Publishing Group Ltd. (Kneller, 2010).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3958165&req=5

f6-bmj-44-4-1007: Public and private initiative contributions to the discovery of new drugs in different countries for the period between 1998 and 2007. Reproduced from Nature Reviews Drug Discovery, November 2010, Vol. 9, Pages 867–882 with permission of Nature Publishing Group Ltd. (Kneller, 2010).

Mentions: Another aspect to be considered is the process of generating new drugs, which identifies the institutions that contribute the most to their generation. Figure 6, for example, illustrates the origin of the 252 new drugs approved by the FDA from 1998 to 2007.


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)

Public and private initiative contributions to the discovery of new drugs in different countries for the period between 1998 and 2007. Reproduced from Nature Reviews Drug Discovery, November 2010, Vol. 9, Pages 867–882 with permission of Nature Publishing Group Ltd. (Kneller, 2010).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6-bmj-44-4-1007: Public and private initiative contributions to the discovery of new drugs in different countries for the period between 1998 and 2007. Reproduced from Nature Reviews Drug Discovery, November 2010, Vol. 9, Pages 867–882 with permission of Nature Publishing Group Ltd. (Kneller, 2010).
Mentions: Another aspect to be considered is the process of generating new drugs, which identifies the institutions that contribute the most to their generation. Figure 6, for example, illustrates the origin of the 252 new drugs approved by the FDA from 1998 to 2007.

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