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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

Biosynthetic pathway for hyaluronic acid in Streptococci. Some intermediates are also required for cell wall synthesis. Important genes are: hasB (coding for UDP-glucose 6-dehygrogenase); hasC (coding for glucose-1-P uridyltransferase); hasA (HA synthase)
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Fig3: Biosynthetic pathway for hyaluronic acid in Streptococci. Some intermediates are also required for cell wall synthesis. Important genes are: hasB (coding for UDP-glucose 6-dehygrogenase); hasC (coding for glucose-1-P uridyltransferase); hasA (HA synthase)

Mentions: In the early 80s, HA started to be produced using the bacteria Streptococci as a host cell. However, the genus Streptococci is known to possess several human pathogens, thus, the HA purification costs using this bacteria genus are elevated. Therefore, other microorganisms, natural producers or genetically engineered ones, have been considered for HA production. Ideally, a perfect microorganism for HA production should have GRAS status (generally regarded as safe), not secrete any toxins and be able to produce the biopolymer continuously so it can reach at least 1 megadalton (MDa). The molecular weight (MW) and the purity of HA are indicative of its quality: polymers that have a greater MW (>0.5 MDa) have greater market value. From the microbial point of view, producing such a polymer is also a challenge because of its high metabolic energy cost. For instance, in order to produce a dimer of HA, three ATP molecules, two UTP molecules, two NAD+ molecules, one molecule of Acetyl-CoA and one molecule of glutamine (counting the energy expended towards glycolysis) are necessary for the synthesis of the two precursors of HA (Fig. 3).Fig. 3


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)

Biosynthetic pathway for hyaluronic acid in Streptococci. Some intermediates are also required for cell wall synthesis. Important genes are: hasB (coding for UDP-glucose 6-dehygrogenase); hasC (coding for glucose-1-P uridyltransferase); hasA (HA synthase)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Biosynthetic pathway for hyaluronic acid in Streptococci. Some intermediates are also required for cell wall synthesis. Important genes are: hasB (coding for UDP-glucose 6-dehygrogenase); hasC (coding for glucose-1-P uridyltransferase); hasA (HA synthase)
Mentions: In the early 80s, HA started to be produced using the bacteria Streptococci as a host cell. However, the genus Streptococci is known to possess several human pathogens, thus, the HA purification costs using this bacteria genus are elevated. Therefore, other microorganisms, natural producers or genetically engineered ones, have been considered for HA production. Ideally, a perfect microorganism for HA production should have GRAS status (generally regarded as safe), not secrete any toxins and be able to produce the biopolymer continuously so it can reach at least 1 megadalton (MDa). The molecular weight (MW) and the purity of HA are indicative of its quality: polymers that have a greater MW (>0.5 MDa) have greater market value. From the microbial point of view, producing such a polymer is also a challenge because of its high metabolic energy cost. For instance, in order to produce a dimer of HA, three ATP molecules, two UTP molecules, two NAD+ molecules, one molecule of Acetyl-CoA and one molecule of glutamine (counting the energy expended towards glycolysis) are necessary for the synthesis of the two precursors of HA (Fig. 3).Fig. 3

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