Disintergration three decades ago allopurinol was considered as

of DNA molecules in human body results in Uric acid, a natural product of
metabolism, which is expelled from the body. But, high accretion of uric acid
in the body and or low elimination rate of it is linked to pathogenesis of uman
diseases such as gout and hyperuricemia. It is affected through the high
consumption of food rich in purine. Hyperuricemia results from an imbalance
between the rates of production and excretion of uric acid. Due to the low
solubility of uric acid, long-term hyperuricemia leads to destructive
crystalline urate deposits around joints, in soft tissues, and in some organs,
causing a number of disorders, including gout and urate nephropathy associated
with tumor lysis syndrome. Studies have also shown that hyperuricemia in humans
can increase the risk of cardiovascular diseases, chronic nephropathy, impaired
renal function, hypertension, and stroke. Due to those severe complications of
hyperuricemia, its therapeutic countermeasures have attracted great attention
in the medical community. This disease afflicts more than 10 million patients
worldwide, and its incidence is on the rise. More than three decades ago
allopurinol was considered as a first line drug which regulate uric acid
synthesis by inhibiting xanthine oxidase (XO) enzyme. Besides to allopurinol,
febuxostat is also used to reduce the synthesis of uric acid by inhibiting the
XO enzyme and is approved by the European Medical Agency in 2008 and US FDA in
2009In contrast to allopurinol it acts on both reduced as well as oxidised form
of XO. Partial relief from inflammation can be obtained by administration of
hydroxychloroquine and nonsteroidal anti -inflammatory drugs. But these drugs
are prone to have enormous side effects, so to regulate the uric acid level in
serum or soft tissues, enzymatic treatment is considered to be the better way
without any side effects. Uricase a tetramer therapeutic enzyme which opens the
purine ring of uric acid and forms allantoin, CO2 and H2O. Allantoin is a
soluble molecule in plasma, which can be eliminated through the kidneys as it
is 5–10 times more soluble than uric acid. Uricase enzyme is conserved present
in mammals, plants, fungi, bacteria and yeasts but is absent in humans due to
evolutionary mutations in uricase gene. Thus, uricase from various
microorganisms has been administered for 40 years to treat hyperuricemia and
gout. Rasburicase, a recombinant form of Uox from Aspergillus flavus, is the
first marketed Uox preparation for the treatment and prophylaxis of acute
hyperuricemia resulting from tumor lysis syndrome in children with cancer. Its
outstanding ability to decrease uric acid level and dissolve tophi makes
Uox-based therapy a more promising strategy for the treatment of hyperuricemia.
But, the clinical use of rasburicase is limited by its immunogenicity and short
half-life . In 2010, pegloticase, a PEGylated chimeric porcine-baboon Uox, was
approved by the USA Food and Drug Administration (FDA) for treatment of chronic
gout in adult patients refractory to conventional therapy. With a higher
sequence homology to hypothetic human uricase and PEGylation, the
immunogenicity of pegloticase is reduced and half-life prolonged. Also to the
FDA approved porcine–baboon chimera, investigations on several other chimeric uricases
have also been reported, such as canine–human chimeric uricase and
porcine–human chimeric uricase. The development of therapeutic uricase for
human use is an intractable challenge as activity, stability, and
immunoreactivity should all be taken into consideration As such, the medical
community has a strong interest in developing a recombinant “human-like”
uricase to treat hyperuricemia and gout. Uricase is localized inside
microorganisms, especially Bacillus pasteurii, Proteus mirabilis, and Escherichia
coli, while other microorganisms could produce them by changing certain
components of the culture media as in Streptomyces albosriseolus,
Microbacterium, Bacillus thermocatenulatus, Candida tropicalis, and Pseudomonas
aeruginosa. Streptomyces exofolitus isolated from soil by Magda et al were
found to be high producer of uricase. 
Uricase is a therapeutic enzyme belonging to the class of the
oxidoreductases, which catalyses the oxidation of uric acid, producing allantoin
and acting in the purine degradation pathway. The enzyme exists as a tetramer
of identical subunits, each containing a possible type 2 copper-binding site.
Urate oxidase is a homotetrameric enzyme containing four identical active sites
situated at the interfaces between its four subunits. It is unique among the
oxidases in that it does not need a metal atom or an organic co-factor for
catalysis.Uricase is useful for enzymatic determination of uric acid in
biological fluids for clinical analysis. Uricase can be also used as a protein
drug to reduce toxic urate accumulation. Immobilized uricase can be used as a
uric acid biosensor. Uricase is also used as an additive in commercial
formulations of hair coloring agents. Although uricase has been produced using
several microbial sources, due to its increasing importance in treatment and in
diagnosis, new sources of uricase are sought aiming to produce better yield of
the enzyme. The largest and most important genus in the order actinomycetales
are Streptomyces. It comprises up to 90% of actinomycetes isolated from the
soil samples, it is prolific producers of bioactive compounds such as
antibiotics and enzymes which have important applications both in medicine and
agriculture. The present study aimid at searching for potential uricase
producing streptomyces source and cloning and expression and purification it.


I'm Mack!

Would you like to get a custom essay? How about receiving a customized one?

Check it out