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Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms.

de Oliveira JD, Carvalho LS, Gomes AM, Queiroz LR, Magalhães BS, Parachin NS - Microb. Cell Fact. (2016)

Bottom Line: With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer.Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production.Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA.

View Article: PubMed Central - PubMed

Affiliation: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, CEP 70.790-160, Brazil.

ABSTRACT
Hyaluronic acid, or HA, is a rigid and linear biopolymer belonging to the class of the glycosaminoglycans, and composed of repeating units of the monosaccharides glucuronic acid and N-acetylglucosamine. HA has multiple important functions in the human body, due to its properties such as bio-compatibility, lubricity and hydrophilicity, it is widely applied in the biomedical, food, health and cosmetic fields. The growing interest in this molecule has motivated the discovery of new ways of obtaining it. Traditionally, HA has been extracted from rooster comb-like animal tissues. However, due to legislation laws HA is now being produced by bacterial fermentation using Streptococcus zooepidemicus, a natural producer of HA, despite it being a pathogenic microorganism. With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer. Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production. Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA.

No MeSH data available.


Related in: MedlinePlus

Evolutionary relationship between HA synthase proteins (HAS) in an identity percentage tree using Jalview 2.9.0b2. Acessions acquired through the NCBI BLAST tool, aiming for better score values in organisms, Homo sapiens, Mus musculus, Xenopus laevis aligned to the Streptococcus pyogenis protein sequence
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Fig4: Evolutionary relationship between HA synthase proteins (HAS) in an identity percentage tree using Jalview 2.9.0b2. Acessions acquired through the NCBI BLAST tool, aiming for better score values in organisms, Homo sapiens, Mus musculus, Xenopus laevis aligned to the Streptococcus pyogenis protein sequence

Mentions: The eukaryotic Class I HA synthases show homology to Class I HA synthases from microorganisms, indicated by up to five conserved transmembrane domains, with a DXD motif in the cytoplasmic region of the glycosyltransferase domain (PFam: PF00535) between the second and third transmembrane, therefore responsible for the binding of UTP-sugars to the enzyme leading to the polymerization of HA. The bacterial HAS demonstrates up to 47 % similarity within 92 % of query cover; this homology is usually attributed to a lateral gene-exchange from the animal host to the bacterium that may have occurred in the past. Figure 4 shows the phylogenetic relationship between streptococcal HAS protein sequences with the most relevant vertebrate model organisms in which HAS proteins have been reported. Hyaluronic acid produced by animals and microbes are extremely different in molecular weight and rate of synthesis, wherein the speed of synthesis in microbes is ten-fold faster than the speed in animals [25, 41]. However, the great similarity between the genes involved in the production of hyaluronic acid of different cells requires a theory for the existence of this sharing. The discovery that Chrlorella virus cells are capable of inducing the production of hyaluronic acid in host cells [42] and the discovery of a has gene into a Bacillus anthracis plasmid confirmed the theory and classification of the gene has as one of the 223 candidates that are capable of lateral gene transfer in bacteria to vertebrates [26], which explains the similarity existing among has genes. On the other hand, the Class II—HAS from Pasteurella multocida (pmHAS)—is different from all other HA synthases, as previously discussed, which is likely to be an example of convergent evolution, a phenomenon in which living organisms develop similar characteristics from different sources, in this case, different enzymes with the same product: HA [43].Fig. 4


Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms.

de Oliveira JD, Carvalho LS, Gomes AM, Queiroz LR, Magalhães BS, Parachin NS - Microb. Cell Fact. (2016)

Evolutionary relationship between HA synthase proteins (HAS) in an identity percentage tree using Jalview 2.9.0b2. Acessions acquired through the NCBI BLAST tool, aiming for better score values in organisms, Homo sapiens, Mus musculus, Xenopus laevis aligned to the Streptococcus pyogenis protein sequence
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930576&req=5

Fig4: Evolutionary relationship between HA synthase proteins (HAS) in an identity percentage tree using Jalview 2.9.0b2. Acessions acquired through the NCBI BLAST tool, aiming for better score values in organisms, Homo sapiens, Mus musculus, Xenopus laevis aligned to the Streptococcus pyogenis protein sequence
Mentions: The eukaryotic Class I HA synthases show homology to Class I HA synthases from microorganisms, indicated by up to five conserved transmembrane domains, with a DXD motif in the cytoplasmic region of the glycosyltransferase domain (PFam: PF00535) between the second and third transmembrane, therefore responsible for the binding of UTP-sugars to the enzyme leading to the polymerization of HA. The bacterial HAS demonstrates up to 47 % similarity within 92 % of query cover; this homology is usually attributed to a lateral gene-exchange from the animal host to the bacterium that may have occurred in the past. Figure 4 shows the phylogenetic relationship between streptococcal HAS protein sequences with the most relevant vertebrate model organisms in which HAS proteins have been reported. Hyaluronic acid produced by animals and microbes are extremely different in molecular weight and rate of synthesis, wherein the speed of synthesis in microbes is ten-fold faster than the speed in animals [25, 41]. However, the great similarity between the genes involved in the production of hyaluronic acid of different cells requires a theory for the existence of this sharing. The discovery that Chrlorella virus cells are capable of inducing the production of hyaluronic acid in host cells [42] and the discovery of a has gene into a Bacillus anthracis plasmid confirmed the theory and classification of the gene has as one of the 223 candidates that are capable of lateral gene transfer in bacteria to vertebrates [26], which explains the similarity existing among has genes. On the other hand, the Class II—HAS from Pasteurella multocida (pmHAS)—is different from all other HA synthases, as previously discussed, which is likely to be an example of convergent evolution, a phenomenon in which living organisms develop similar characteristics from different sources, in this case, different enzymes with the same product: HA [43].Fig. 4

Bottom Line: With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer.Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production.Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA.

View Article: PubMed Central - PubMed

Affiliation: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, CEP 70.790-160, Brazil.

ABSTRACT
Hyaluronic acid, or HA, is a rigid and linear biopolymer belonging to the class of the glycosaminoglycans, and composed of repeating units of the monosaccharides glucuronic acid and N-acetylglucosamine. HA has multiple important functions in the human body, due to its properties such as bio-compatibility, lubricity and hydrophilicity, it is widely applied in the biomedical, food, health and cosmetic fields. The growing interest in this molecule has motivated the discovery of new ways of obtaining it. Traditionally, HA has been extracted from rooster comb-like animal tissues. However, due to legislation laws HA is now being produced by bacterial fermentation using Streptococcus zooepidemicus, a natural producer of HA, despite it being a pathogenic microorganism. With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer. Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production. Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA.

No MeSH data available.


Related in: MedlinePlus