Improvement of production of Kojic acid by a mutant strain Aspergillus oryzae, MK107-39

Futamura, Takafumi; Okabe, Mitsuyasu; Tamura, Takayoshi; Toda, Kyouko; Matsunobu, Toshio; Park, Yong Soo

doi:10.1016/s1389-1723(01)80133-x

Cited by 26 publications

(4 citation statements)

References 5 publications

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“…Although this may not be directly suitable for industrial application, the antibody productivity by A. oryzae can be further improved by several rounds of mutagenesis and additional genetic modifications such as deletion of other protease genes, optimizations involving protein secretion and the increasing of copy-number for heavy and light chains. Moreover, a further enhanced productivity is also expected with the controlled growth environment employing a bioreactor as previously reported in A. oryzae [41], which will meet the industrially competitive level.…”

Section: Discussionmentioning

confidence: 74%

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Huynh

Morita

Sakamoto

et al. 2020

Fungal Biol Biotechnol

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Background: Monoclonal antibodies (mAbs) as biopharmaceuticals take a pivotal role in the current therapeutic applications. Generally mammalian cell lines, such as those derived from Chinese hamster ovaries (CHO), are used to produce the recombinant antibody. However, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. Aspergillus oryzae, a filamentous fungus recognized as a GRAS (Generally Regarded As Safe) organism, has an ability to secrete a large amount of proteins into the culture supernatant, and thus the fungus has been used as one of the cost-effective microbial hosts for heterologous protein production. Pursuing this strategy the human anti-TNFα antibody adalimumab, one of the world's best-selling antibodies for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis, was chosen to produce the full length of mAbs by A. oryzae. Generally, N-glycosylation of the antibody affects immune effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) via binding to the Fc receptor (FcγR) on immune cells. The CRISPR/Cas9 system was used to first delete the Aooch1 gene encoding a key enzyme for the hyper-mannosylation process in fungi to investigate the binding ability of antibody with FcγRIIIa.Results: Adalimumab was expressed in A. oryzae by the fusion protein system with α-amylase AmyB. The full-length adalimumab consisting of two heavy and two light chains was successfully produced in the culture supernatants. Among the producing strains, the highest amount of antibody was obtained from the ten-protease deletion strain (39.7 mg/L). Two-step purifications by Protein A and size-exclusion chromatography were applied to obtain the high purity sample for further analysis. The antigen-binding and TNFα neutralizing activities of the adalimumab produced by A. oryzae were comparable with those of a commercial product Humira ® . No apparent binding with the FcγRIIIa was detected with the recombinant adalimumab even by altering the N-glycan structure using the Aooch1 deletion strain, which suggests only a little additional activity of immune effector functions. Conclusion:These results demonstrated an alternative low-cost platform for human antibody production by using A. oryzae, possibly offering a reasonable expenditure for patient's welfare.

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Section: Discussionmentioning

confidence: 74%

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Huynh

Morita

Sakamoto

et al. 2020

Fungal Biol Biotechnol

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“…Each one of these factors will be different for each producer microorganism, even with the A. oryzae producer strain itself, where production times can be extended up to 20 days with temperatures of 40 • C, generating amounts of KA of 0.2 g/L [22], although, KA production of up to 42 g/L has been reported [46]. Other authors have reported favorable production in ranges of 25 • C to 30 • C [47]. For example, Rasmey and Abdel-Kareem [43] reported that with temperature peaks above 30 • C, there was a decrease in KA from 68 g/L to 0.5 g/L of KA with A. oryzae, and above temperatures of 45 • C, production reached 0 g/L.…”

Section: Discussionmentioning

confidence: 99%

Production of Kojic Acid by Aspergillus niger M4 with Different Concentrations of Yeast Extract as a Nitrogen Source

et al. 2023

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In agro-industrial processes, microorganisms that are not pathogenic and that generate molecules are generally recognized as safe (GRAS). The Aspergillus niger fungus has different industrial applications, being used to produce citric acid and 166 other secondary metabolites. The objective of this research was to optimize a culture medium to induce the production of kojic acid (KA) by the Aspergillus niger M4 strain in a liquid fermentation process. Four fermentative kinetics were developed in flasks, using different levels of yeast extract in (1) 0.05 g/L, (2) 0.10 g/L, (3) 2.5 g/L, and (4) 2.5 g/L + Zinc sulfate. The culture medium conditions influenced the formation and speed of biomass and the synthesis and yield of KA. The optimum production points were from 72 h and 96 h with 0.552 g/L and 0.510 g/L of KA using 2.5 g/L of yeast extract and with a pH of 5.5. The Aspergillus niger M4 strain had the ability to produce kojic acid, which was induced by the concentration of the nitrogen source.

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“…These results agreed exactly with the early results found by May et al (1931). Kojic acid synthesis only started after growth reached stationary phase and stopped when glucose in the medium was depleted (Kitada et al 1967, Megalla et al1985, Rosfarizan et al 1998, Futamura et al 2001. Rosfarizan& and El-Aasar (2006) reported that the excess concentration of carbon source affects the production of kojic acid and resulted in significant Fermentation medium increase in residual sugar due to the inability of fungi to metabolize high levels of sugar.…”

Section: Effect Of Sugar Concentration On Kojic Acid Productionmentioning

confidence: 99%

Isolation and screening of kojic acid producing isolate of Aspergillus oryzae potentially applicable for production from sugarcane molasses

Rasmey¹,

Basha²

2016

IJBR

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Kojic acid is an organic acid produced as secondary metabolite by different fungi specially Aspergillus species. Isolation of a novel fungal strain potential for kojic acid production from agro-industrial wastes was the main purpose of the present study. Kojic acid was estimated in the current investigation colorimetric by 2,6-dichlorophenolindophenol (DCIP). A total of 43 fungal isolates belonging to seven species of Aspergillus recovered from stored wheat grains and dust air were screened for their ability to produce kojic acid. Ten isolates of them belonging to A. oryzae and A. flavus var. columnaris produced high concentrations (16.818 ± 0.006 -43.917 ± 0.389 g/l) of kojic acid from glucose. The secondary screening of these ten isolates for kojic acid production from glucose, sucrose, starch, maltose and cellulose as different carbon sources resulted that A. oryzae 124A was the highly producer on glucose and sucrose recording 44.189 ± 0.079 and 32.135 ± 0.298 g/l, respectively. A. oryzae 124A produced 15.022 ± 0.017 g/l of kojic acid from the pretreated semisynthetic sugarcane molasses. The maximum concentration (29.431 ± 0.001 g/l) of kojic acid production by A. oryzae 124A from sugarcane molasses was obtained when the fungus grown on 5 % sugarcane molasses adjusted at pH 3.5 and incubated at 28 ∘ C for 19 days. The recorded results suggested that A. oryzae 124A could be used as a promising candidate for utilization in kojic acid fermentation from sugarcane molasses on industrial scale.

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Improvement of production of Kojic acid by a mutant strain Aspergillus oryzae, MK107-39

Cited by 26 publications

References 5 publications

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Production of Kojic Acid by Aspergillus niger M4 with Different Concentrations of Yeast Extract as a Nitrogen Source

Isolation and screening of kojic acid producing isolate of Aspergillus oryzae potentially applicable for production from sugarcane molasses

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