enzyme activators


Summary: Compounds or factors that act on a specific enzyme to increase its activity.

Top Publications

  1. Hawley S, Fullerton M, Ross F, Schertzer J, Chevtzoff C, Walker K, et al. The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 2012;336:918-22 pubmed publisher
    ..Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans. ..
  2. Deniro M, Al Mohanna F. Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy. PLoS ONE. 2012;7:e50360 pubmed publisher
    ..Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases. ..
  3. Lian Z, Li Y, Gao J, Qu K, Li J, Hao L, et al. A novel AMPK activator, WS070117, improves lipid metabolism discords in hamsters and HepG2 cells. Lipids Health Dis. 2011;10:67 pubmed publisher
    ..In vitro and in vivo studies suggested that WS070117 may regulate lipid metabolism through stimulating the activation of AMPK and its downstream pathways. ..
  4. Anastasiou D, Poulogiannis G, Asara J, Boxer M, Jiang J, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science. 2011;334:1278-83 pubmed publisher
    ..Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress. ..
  5. Frey R, Mück W, Unger S, Artmeier Brandt U, Weimann G, Wensing G. Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers. J Clin Pharmacol. 2008;48:1400-10 pubmed publisher
    ..Plasma concentrations declined below 1.0 microg/L within 30 minutes of cessation of infusion. Cinaciguat had potent cardiovascular effects reducing preload and afterload, warranting further investigation in patients with heart failure. ..
  6. Costa L, Giordano G, Furlong C. Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on. Biochem Pharmacol. 2011;81:337-44 pubmed publisher
  7. Jiang J, Boxer M, Vander Heiden M, Shen M, Skoumbourdis A, Southall N, et al. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett. 2010;20:3387-93 pubmed publisher
    ..These agents represent the second reported chemotype for activation of PKM2. ..
  8. Nelson T, Cui C, Luo Y, Alkon D. Reduction of beta-amyloid levels by novel protein kinase C(epsilon) activators. J Biol Chem. 2009;284:34514-21 pubmed publisher
  9. Roger S, Paysant J, Badier Commander C, Cordi A, Verbeuren T, Feletou M. Anti-aggregating effect of BAY 58-2667, an activator of soluble guanylyl cyclase. Vascul Pharmacol. 2010;53:281-7 pubmed publisher
    ..When the sGC is oxidized, BAY 58-2667 becomes a relevant anti-aggregating agent, which synergizes with the cAMP-dependent pathway. ..

More Information


  1. Sajan M, Bandyopadhyay G, Miura A, Standaert M, Nimal S, Longnus S, et al. AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC. Am J Physiol Endocrinol Metab. 2010;298:E179-92 pubmed publisher
    ..On the other hand, although aPKC is activated by treadmill exercise, this activation is not required for exercise-induced increases in glucose transport, and therefore may be a redundant mechanism. ..
  2. Hoffmann L, Schmidt P, Keim Y, Schaefer S, Schmidt H, Stasch J. Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation. Br J Pharmacol. 2009;157:781-95 pubmed publisher
  3. Knorr A, Hirth Dietrich C, Alonso Alija C, HARTER M, Hahn M, Keim Y, et al. Nitric oxide-independent activation of soluble guanylate cyclase by BAY 60-2770 in experimental liver fibrosis. Arzneimittelforschung. 2008;58:71-80 pubmed publisher
    ..Nitric oxide-independent activation of sGC might be an innovative therapeutic approach for the treatment of liver fibrosis of necro-inflammatory and immunological origin. ..
  4. Báu F, Mónica F, Priviero F, Baldissera L, De Nucci G, Antunes E. Evaluation of the relaxant effect of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in isolated detrusor smooth muscle. Eur J Pharmacol. 2010;637:171-7 pubmed publisher
    ..In conclusion, rabbit detrusor smooth muscle relaxations by BAY 41-2272 involve mainly cGMP production, but an additional mechanism involving Ca(2+) influx blockade independently of cGMP production appears to be involved...
  5. Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard B, et al. SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem. 2010;285:32695-703 pubmed publisher
    ..Varghese, A., Ward, J., Withka, J., and Ahn, K. (2010) J. Biol. Chem. 285, 8340-8351). Rather, the data suggest that STACs interact directly with SIRT1 and activate SIRT1-catalyzed deacetylation through an allosteric mechanism. ..
  6. Hongpaisan J, Sun M, Alkon D. PKC ? activation prevents synaptic loss, A? elevation, and cognitive deficits in Alzheimer's disease transgenic mice. J Neurosci. 2011;31:630-43 pubmed publisher
    ..These results suggest that synaptic loss and the resulting cognitive deficits depend on the balance between the lowering effects of A? on PKC ? and ? versus the lowering effects of PKC on A? in AD transgenic mice. ..
  7. Li S, Shin D, Chun Y, Lee M, Kim M, Park J. A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. Mol Cancer Ther. 2008;7:3729-38 pubmed publisher
    ..Given these results, we suggest that the functional inactivation of HIF-alpha contributes to the YC-1-induced deregulation of hypoxia-induced genes. ..
  8. Marugan J, Zheng W, Motabar O, Southall N, Goldin E, Sidransky E, et al. Evaluation of 2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one analogues as GAA activators. Eur J Med Chem. 2010;45:1880-97 pubmed publisher
    ..b>Enzyme activators with chaperone activity would be even more desirable as they would not inhibit the enzyme after ..
  9. Cabrol C, Huzarska M, Dinolfo C, Rodriguez M, Reinstatler L, Ni J, et al. Small-molecule activators of insulin-degrading enzyme discovered through high-throughput compound screening. PLoS ONE. 2009;4:e5274 pubmed publisher
    ..Several larger lessons abstracted from this screen will help inform the design of future screening campaigns and facilitate the eventual development of IDE activators with therapeutic utility. ..
  10. Vu C, Bemis J, Disch J, Ng P, Nunes J, Milne J, et al. Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators. J Med Chem. 2009;52:1275-83 pubmed publisher
    ..The most potent analogue within this series, namely, compound 29, has demonstrated oral antidiabetic activity in the ob/ob mouse model, the diet-induced obesity (DIO) mouse model, and the Zucker fa/fa rat model. ..
  11. Martin F, Baskaran P, Ma X, Dunten P, Schaefer M, Stasch J, et al. Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase. J Biol Chem. 2010;285:22651-7 pubmed publisher
    ..The structure provides insights into how BAY 58-2667 binds and activates sGC to rescue heme-NO dysfunction in cardiovascular diseases...
  12. Fenton A. Identification of allosteric-activating drug leads for human liver pyruvate kinase. Methods Mol Biol. 2012;796:369-82 pubmed publisher
    ..Using hL-PYK, we demonstrate the potential of drug library screens to identify allosteric-activator drug leads. ..
  13. Zhan X, Stoy H, Kaoud T, Perry N, Chen Q, Perez A, et al. Peptide mini-scaffold facilitates JNK3 activation in cells. Sci Rep. 2016;6:21025 pubmed publisher
    ..The arrestin-3 peptide is the smallest MAPK scaffold known. This peptide or its mimics can regulate MAPKs, affecting cellular decisions to live or die. ..
  14. Holmuhamedov E, Czerny C, Beeson C, Lemasters J. Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde. J Biol Chem. 2012;287:7692-700 pubmed publisher
    ..In conclusion, AcAld, derived from ethanol metabolism, suppresses ureagenesis in hepatocytes mediated by closure of VDAC...
  15. Morizane Y, Thanos A, Takeuchi K, Murakami Y, Kayama M, Trichonas G, et al. AMP-activated protein kinase suppresses matrix metalloproteinase-9 expression in mouse embryonic fibroblasts. J Biol Chem. 2011;286:16030-8 pubmed publisher
    ..Overall, our results suggest that both AMPK? isoforms suppress MMP-9 expression and that both the activity and presence of AMPK? contribute to its function as a regulator of MMP-9 expression by inhibiting the NF-?B pathway. ..
  16. Goetzl S, Teutloff C, Werther T, Hennig S, Jeoung J, Bittl R, et al. Protein Dynamics in the Reductive Activation of a B12-Containing Enzyme. Biochemistry. 2017;56:5496-5502 pubmed publisher
  17. Singh R, Mandal T, Balsubramanian N, Viaene T, Leedahl T, Sule N, et al. Histone deacetylase activators: N-acetylthioureas serve as highly potent and isozyme selective activators for human histone deacetylase-8 on a fluorescent substrate. Bioorg Med Chem Lett. 2011;21:5920-3 pubmed publisher
    ..The experimental data reveals that such activating feature is manifested via decrease in the K(m) value of the enzyme's substrate and increase in the catalytic turnover rate of the enzyme. ..
  18. Li G, Liu Y, Zhu Y, Liu A, Xu Y, Li X, et al. ACE2 activation confers endothelial protection and attenuates neointimal lesions in prevention of severe pulmonary arterial hypertension in rats. Lung. 2013;191:327-36 pubmed publisher
  19. Lasker G, Maley J, Pankey E, Kadowitz P. Targeting soluble guanylate cyclase for the treatment of pulmonary hypertension. Expert Rev Respir Med. 2011;5:153-61 pubmed publisher
  20. Tulipano G, Faggi L, Losa M, Mortini P, Spinello M, Sibilia V, et al. Effects of AMPK activation and combined treatment with AMPK activators and somatostatin on hormone secretion and cell growth in cultured GH-secreting pituitary tumor cells. Mol Cell Endocrinol. 2013;365:197-206 pubmed publisher
    ..Moreover, AICAR and SS-14 reduced ERK phosphorylation with a different time course. The combined treatment reduced phospho-ERK levels at any time point. ..
  21. Choi S, Kim M, Joo K, Park S, Kim J, Jung J, et al. Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism. Pharmacol Res. 2012;66:51-9 pubmed publisher
    ..1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator. ..
  22. Cho S, Jeong E, Lee J, Kim H, Lim J, Kim C, et al. Doxorubicin induces the persistent activation of intracellular transglutaminase 2 that protects from cell death. Mol Cells. 2012;33:235-41 pubmed publisher
    ..Our findings indicate that the persistent activation of TG2 by doxorubicin contributes to cell survival, suggesting that the mechanism-based inhibition of TG2 may be a novel strategy to prevent drug-resistance in doxorubicin treatment...
  23. Raj H, Puthan Veetil V, Szymanski W, Dekker F, Quax W, Feringa B, et al. Characterization of a thermostable methylaspartate ammonia lyase from Carboxydothermus hydrogenoformans. Appl Microbiol Biotechnol. 2012;94:385-97 pubmed publisher
    ..This newly identified thermostable MAL appears to be a potentially attractive biocatalyst for the stereoselective synthesis of aspartic acid derivatives on large (industrial) scale. ..
  24. Wang Y, Yang D, Song L, Li T, Yang J, Zhang X, et al. Mifepristone-inducible caspase-1 expression in mouse embryonic stem cells eliminates tumor formation but spares differentiated cells in vitro and in vivo. Stem Cells. 2012;30:169-79 pubmed publisher
    ..These results suggest that this novel ESC-based therapy can be used in Parkinson's disease and other related disorders without the risk of tumor formation. ..
  25. Zhou X, Wu J. Heterologous expression and characterization of Bacillus coagulans L-arabinose isomerase. World J Microbiol Biotechnol. 2012;28:2205-12 pubmed publisher
    ..L: -ribulose (97 g/L) was obtained from 500 g/l of L: -arabinose catalyzed by the enzyme (8.3 U/mL) under the optimal conditions within 1.5 h, giving at a substrate conversion of 19.4% and a production rate of 65 g L(-1) h(-1). ..
  26. Mohan Kumar N, Manonmani H. Purification, characterization and kinetic properties of extracellular L-asparaginase produced by Cladosporium sp. World J Microbiol Biotechnol. 2013;29:577-87 pubmed publisher
    ..69 h. The enzyme inhibited acrylamide formation in potato chips by 96 % making it a potential candidate for food industry to reduce acrylamide content in starchy fried food commodities. ..
  27. Stringer B, Udofa E, Antalis T. Regulation of the human plasminogen activator inhibitor type 2 gene: cooperation of an upstream silencer and transactivator. J Biol Chem. 2012;287:10579-89 pubmed publisher
    ..These data suggest a model for the transcriptional control of the human PAI-2 gene and further our understanding of the molecular basis for its tissue-specific expression. ..
  28. Rabasseda X. A report from the 47th European Association for the Study of Diabetes annual meeting (September 12-16, 2011 - Lisbon, Portugal). Drugs Today (Barc). 2011;47:923-34 pubmed publisher
    ..New findings with currently available drugs and drugs in research that were reported during this year's EASD meeting in the beautiful city of Lisbon are summarized in the following report. ..
  29. Bei Y, Song Y, Wang F, Dimitrova Shumkovska J, Xiang Y, Zhao Y, et al. miR-382 targeting PTEN-Akt axis promotes liver regeneration. Oncotarget. 2016;7:1584-97 pubmed publisher
    ..Collectively, our findings identify miR-382 as a promoter for hepatocyte proliferation and cell growth via targeting PTEN-Akt axis which might be a novel therapeutic target to enhance liver regeneration capability. ..
  30. McIntosh V, Chandrasekera P, Lasley R. Sex differences and the effects of ovariectomy on the ?-adrenergic contractile response. Am J Physiol Heart Circ Physiol. 2011;301:H1127-34 pubmed publisher
    ..The ?-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A(1)AR may contribute to these sex differences. ..
  31. Donmez G, Outeiro T. SIRT1 and SIRT2: emerging targets in neurodegeneration. EMBO Mol Med. 2013;5:344-52 pubmed publisher
    ..We also cover the role of SIRT1 in neuronal differentiation due to the possible implications in neurodegenerative conditions, and conclude with an outlook on the potential therapeutic value of SIRT1 and SIRT2 in these disorders. ..
  32. Campbell M, Underbakke E, Potter C, Carragher B, Marletta M. Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase. Proc Natl Acad Sci U S A. 2014;111:2960-5 pubmed publisher
    ..The molecular architecture and pronounced flexibility observed provides a significant step forward in understanding the mechanism of NO signaling. ..
  33. Zhang J, Cui J, Yin T, Sun L, Li G. Activated effect of lignin on ?-amylase. Food Chem. 2013;141:2229-37 pubmed publisher
    ..This work will give a deeper insight into lignin as a kind of dietary fibre, known as an important food functional factor. Furthermore, it also contributes to the exploration of an activator of ?-amylase, used in the food industry. ..
  34. Tichon A, Eitan E, Kurkalli B, Braiman A, Gazit A, Slavin S, et al. Oxidative stress protection by novel telomerase activators in mesenchymal stem cells derived from healthy and diseased individuals. Curr Mol Med. 2013;13:1010-22 pubmed
    ..These results suggest that pharmaceutical increase of telomerase may confer a beneficial therapeutic advantage in regenerative medicine when hMSC therapy is applied. ..
  35. Vincent V, Aghajari N, Pollet N, Boisson A, Boudebbouze S, Haser R, et al. The acid tolerant and cold-active ?-galactosidase from Lactococcus lactis strain is an attractive biocatalyst for lactose hydrolysis. Antonie Van Leeuwenhoek. 2013;103:701-12 pubmed publisher
    ..0 to 5.5) and high temperatures (55 and 60 °C). The bioconversion of lactose using the L. lactis ?-galactosidase allows the production of lactose with a high bioconversion rate (98 %) within a wide range of pH and temperature. ..
  36. Weinheimer I, Boonrod K, Moser M, Wassenegger M, Krczal G, Butcher S, et al. Binding and processing of small dsRNA molecules by the class 1 RNase III protein encoded by sweet potato chlorotic stunt virus. J Gen Virol. 2014;95:486-95 pubmed publisher
    ..5, whereas ds-siRNA was processed more efficiently at pH 8.5. The results revealed factors that influence binding and processing of small dsRNA substrates by class 1 RNase III in vitro or make them unsuitable for processing by the enzyme...
  37. Huh J, Kim S, Lee J, Lee Y. YC-1 attenuates hypoxia-induced pulmonary arterial hypertension in mice. Pulm Pharmacol Ther. 2011;24:638-46 pubmed publisher
    ..Therefore, these data imply that YC-1 has therapeutic potential for use in a single or combination therapy for PAH. ..
  38. Chaneton B, Hillmann P, Zheng L, Martin A, Maddocks O, Chokkathukalam A, et al. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature. 2012;491:458-462 pubmed publisher
    ..This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation. ..
  39. Chen S, Ye F, Chen Y, Chen Y, Zhao H, Yatsunami R, et al. Biochemical analysis and kinetic modeling of the thermal inactivation of MBP-fused heparinase I: implications for a comprehensive thermostabilization strategy. Biotechnol Bioeng. 2011;108:1841-51 pubmed publisher
  40. Min K, Kim S, Yum T, Kim Y, Sang B, Um Y. Conversion of levulinic acid to 2-butanone by acetoacetate decarboxylase from Clostridium acetobutylicum. Appl Microbiol Biotechnol. 2013;97:5627-34 pubmed publisher
    ..The results in this study are significant in the development of a renewable method for the synthesis of 2-butanone from biomass-derived chemical, levulinic acid, through enzymatic decarboxylation...
  41. Hui K, Arnot M, Shin H, Sun H, Feng Z. Differential regulation of low and high voltage-activated calcium channels in neonatal rat myocytes following chronic PKA modulation. Channels (Austin). 2011;5:357-66 pubmed publisher
    ..PKA is a key target of ?-adrenoceptor activiation, thus, our findings suggest long-term repeated use of ?-adrenergic drugs may induce unexpected functional alteration of VDCCs. ..
  42. Nogueiras R, Habegger K, Chaudhary N, Finan B, Banks A, Dietrich M, et al. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev. 2012;92:1479-514 pubmed publisher
    ..Consequently, activation of sirtuins by genetic or pharmacological means can elicit multiple metabolic benefits that protect mice from diet-induced obesity, type 2 diabetes, and nonalcoholic fatty liver disease. ..
  43. Dutta K, Krishnamoorthy H, Venkata Dasu V. Novel cutinase from Pseudomonas cepacia NRRL B 2320: purification, characterization and identification of cutinase encoding genes. J Gen Appl Microbiol. 2013;59:171-84 pubmed
    ..Two cutinase encoding genes were identified in P. cepacia, cloned and expressed in E. coli BL21 (DE3). ..
  44. Stevens B, Litchfield J, Pfefferkorn J, Atkinson K, Perreault C, Amor P, et al. Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia. Bioorg Med Chem Lett. 2013;23:6588-92 pubmed publisher
    ..This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. ..
  45. Cheruvallath Z, Gwaltney S, Sabat M, Tang M, Wang H, Jennings A, et al. Discovery of potent and orally active 1,4-disubstituted indazoles as novel allosteric glucokinase activators. Bioorg Med Chem Lett. 2017;27:2678-2682 pubmed publisher
    ..anti-diabetic OGTT efficacy was demonstrated with 29 in a rodent models of type 2 diabetes. ..
  46. Boehlein S, Shaw J, Hwang S, Stewart J, Curtis Hannah L. Deciphering the kinetic mechanisms controlling selected plant ADP-glucose pyrophosphorylases. Arch Biochem Biophys. 2013;535:215-26 pubmed publisher
    ..Finally, ADP-Glc the physiologically relevant product of this enzyme has complex, isoform-specific effects on catalysis. ..
  47. Sabino D, Brown N, Basto R. Drosophila Ajuba is not an Aurora-A activator but is required to maintain Aurora-A at the centrosome. J Cell Sci. 2011;124:1156-66 pubmed publisher
    ..On the basis of our studies in Drosophila neuroblasts, we propose that a key function of Ajuba, in these cells, is to maintain active Aur-A at the centrosome during mitosis. ..
  48. Zhao T, Zhang L, Liu J, Guo T. Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by anisomycin. Am J Physiol Heart Circ Physiol. 2012;303:H1263-72 pubmed publisher
    ..Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection. ..
  49. Vazquez Roque M, Camilleri M. Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation. Expert Rev Gastroenterol Hepatol. 2011;5:301-10 pubmed publisher
    ..From animal studies to human pharmacodynamic Phase Ib trials, and a comprehensive program of Phase IIb and III trials in health and disease, linaclotide demonstrates long-term efficacy and safety in CC and IBS-C. ..
  50. Dagda R, Gusdon A, Pien I, Strack S, Green S, Li C, et al. Mitochondrially localized PKA reverses mitochondrial pathology and dysfunction in a cellular model of Parkinson's disease. Cell Death Differ. 2011;18:1914-23 pubmed publisher
    ..These data indicate that redirecting endogenous PKA to mitochondria can compensate for deficiencies in PINK1 function, highlighting the importance of compartmentalized signaling networks in mitochondrial quality control. ..
  51. Sehgal S, Khattak N, Mir A. Structural, phylogenetic and docking studies of D-amino acid oxidase activator (DAOA), a candidate schizophrenia gene. Theor Biol Med Model. 2013;10:3 pubmed publisher
    ..There is an urgent need to develop effective drugs for schizophrenia, and tools for examining candidate genes more accurately and efficiently are required. ..
  52. Zhao W, Huang Y, Liu Z, Cao B, Peng Y, Qiu Y. Dopamine receptors modulate cytotoxicity of natural killer cells via cAMP-PKA-CREB signaling pathway. PLoS ONE. 2013;8:e65860 pubmed publisher
    ..The results may provide more targets of therapeutic strategy for neuroimmune diseases. ..
  53. Sambasiva Rao K, Tripathy N, Mahalaxmi Y, Prakasham R. Laccase- and peroxidase-free tyrosinase production by isolated microbial strain. J Microbiol Biotechnol. 2012;22:207-14 pubmed
    ..Among all the studied physiological parameters, agitation played a significant role on tyrosinase production. Upon optimization of the parameters, the yield of tyrosinase was improved more than 100% compared with the initial yield. ..