High-level production of a peroxisomal enzyme: Aspergillus flavus uricase accumulates intracellularly and is active in Saccharomyces cerevisiae

Leplatois, Pascal; Douarin, Bertrand Le; Loison, Gérard

doi:10.1016/0378-1119(92)90041-m

Cited by 42 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genes encoding uricase have been cloned from A. flavus, A. nidulans, C. utilis, Arthrobacter globiformis, Cellulomonas flavigena and symbiont of Nilaparvata lugens (Suzuki et al 2004), and expressed in Escherichia coli (Li et al 2006). Uricase from A. flavus was expressed in the yeast S. cerevisiae in a soluble and active form (Leplatois et al 1992). However, the recombinant uricase from E. coli or S. cerevisiae still has the problem with low productivity and cost-effective separation for medical applications (Li et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Chen

Wang

et al. 2008

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Uricase is an important medical enzyme which can be used to determine urate in clinical analysis, to therapy gout, hyperuricemia, and tumor lysis syndrome. Uricase of Candida utilis was successfully expressed in Hansenula polymorpha under the control of methanol oxidase promoter using Saccharomyces cerevisiae α-factor signal peptide as the secretory sequence. Recombinant H. polymorpha MU200 with the highest extracellular uricase production was characterized with three copies of expression cassette and selected for process optimization for the production of recombinant enzyme. Among the parameters investigated in shaking flask cultures, the pH value of medium and inoculum size had great influence on the recombinant uricase production. The maximum extracellular uricase yield of 2.6 U/ml was obtained in shaking flask culture. The yield of recombinant uricase was significantly improved by the combined use of a high cell-density cultivation technique and a pH control strategy of switching culture pH from 5.5 to 6.5 in the induction phase. After induction for 58 h, the production of recombinant uricase reached 52.3 U/ml (about 2.1 g/l of protein) extracellularly and 60.3 U/ml (about 2.4 g/l) intracellularly in fed-batch fermentation, which are much higher than those expressed in other expression systems. To our knowledge, this is the first report about the heterologous expression of uricase in H. polymorpha.

show abstract

Section: Introductionmentioning

confidence: 99%

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Chen

Wang

et al. 2008

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…[188][189][190][191][192][193][194] It is widely used to avoid TLS in patients with Burkett's lymphoma, ALL and AML. Severe allergic reactions and anaphylactic shock are rarely observed.…”

Section: Prevention Of Uric Acid Overproduction Relies On Allopurinolmentioning

confidence: 99%

Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002

Larson

Schiffer

et al. 2003

Leukemia

View full text Add to dashboard Cite

Novel approaches have been designed to treat leukemia based on our understanding of the genetic and biochemical lesions present in different malignancies. This meeting report summarizes some of the recent advances in leukemia treatment. Based on the discoveries of cellular oncogenes, chromosomal translocations, monoclonal antibodies, multidrug resistance pumps, signal transduction pathways, genomics/proteonomic approaches to clinical diagnosis and mutations in biochemical pathways, clinicians and basic scientists have been able to identify the particular genetic mutations and signal transduction pathways involved as well as design more appropriate treatments for the leukemia patient. This meeting report discusses these exciting new therapies and the results obtained from ongoing clinical trials. Furthermore, rational approaches to treat complications of tumor lysis syndrome by administration of the recombinant urate oxidase protein, also known as rasburicase, which corrects the biochemical defect present in humans, were discussed. Clearly, over the past 25 years, molecular biology and biotechnology has provided the hematologist/oncologist novel bullets in their arsenal that will allow treatment by design in leukemia.

show abstract

“…The approved dosing regimen is 0.15 or 0.2 mg·kg -1 ·d -1 for 5 d intravenously (iv) over 30 min [4] . Rasburicase, derived from Aspergillus flavus, is produced by a genetically modified Saccharomyces cerevisiae strain with a long culture period and high price [4,5] . Therefore, low-cost preparation for uricase seems essential.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic analysis of intravenous recombinant urate oxidase using an indirect pharmacological response model in healthy subjects

Cai

Zhang

et al. 2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Pharmacodynamic analysis of intravenous recombinant urate oxidase produced by Escherichia coli was performed in healthy subjects using a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: A randomized, single-blind, placebo-controlled study was performed in 40 healthy Chinese subjects (4 groups of 10 subjects each, placebo 4:1 ratio) who received infusions of uricase (single doses of 0.1, 0.2, and 0.3 mg/kg; multiple doses of 0.2 mg·kg -1 ·d -1 for 7 d). PK profiles were determined through plasma uricase activity, and PD profiles were established using uric acid levels in plasma and urine. The plasma PD parameter was estimated as changes in plasma uric acid levels as the effect in the indirect response model. Adverse events were also monitored. Results: A two-compartment PK model with constant iv input and first-order output was used to describe the kinetic process of plasma uricase. The low value (2.8 U/L) of drug concentration that achieved 50% of maximum effect (EC 50 ) indicated that low plasma uricase concentrations were sufficient to produce pharmacological effects. A strong relationship (r 2 =0.9991) between the mean uric acid concentration in blood and the mean uric acid excretion rate in urine in the range of 11 to 30 h after single dosing was found. Infusions of uricase were well tolerated in all subjects. Conclusion:The PK/PD model predicted the effective dose to be 0.1 mg/kg in healthy subjects. The excretion rate of uric acid in urine may be used as a new index for pharmacological effects in further clinical trials.

show abstract

High-level production of a peroxisomal enzyme: Aspergillus flavus uricase accumulates intracellularly and is active in Saccharomyces cerevisiae

Cited by 42 publications

References 32 publications

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002

Pharmacodynamic analysis of intravenous recombinant urate oxidase using an indirect pharmacological response model in healthy subjects

Contact Info

Product

Resources

About