Process development for scale-up production of a therapeutic L-asparaginase by Streptomyces brollosae NEAE-115 from shake flasks to bioreactor

El‐Naggar, Noura El‐Ahmady; Moawad, Hassan; El-Shweihy, Nancy M.; El-Ewasy, Sara M.; Elsehemy, Islam A.; Abdelwahed, Nayera A. M.

doi:10.1038/s41598-019-49709-6

Cited by 34 publications

(17 citation statements)

References 34 publications

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“…Thus, Taxol was considered as one of the most important additions to the chemotherapeutic field in the late 20th century. The chronology of Taxol discovery, development and its clinical trials has been documented [ 23 , 30 , 32 , 33 , 34 ]. In the late 1980s, diterpenoid Taxane or Taxoid derivatives, Taxol and Docetaxel were introduced and proved to be effective in treatment of a variety of solid tumors including ovarian, lung, breast and bladder cancers [ 35 ].…”

Section: Chronology Of Taxol Its Derivatives As Antiproliferativementioning

confidence: 99%

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Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

et al. 2020

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Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids “Taxol” is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.

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Section: Chronology Of Taxol Its Derivatives As Antiproliferativementioning

confidence: 99%

“…Downregulation of the expression of Taxol genes upon subculturing of the endophytic fungi was reported frequently [ 29 ]. Thus, searching for novel fungal saprophytes having a stable molecular machinery system for conceivable production of Taxol independently is the ultimate objective for biotechnologists [ 22 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

et al. 2020

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“…Carbon sources are essential components in constructing cellular materials and are also used as energy sources [ 32 ]. Several earlier studies revealed the importance of additional nitrogen, carbon, and ion sources in the augmented production of this enzyme [ 33 ]. The organism Enterobacter aerogenes showed maximum l -asparaginase production in the presence of diammonium hydrogen phosphate and sodium citrate as nitrogen and carbon sources, respectively [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Response surface methodological optimization of l-asparaginase production from the medicinal plant endophyte Acinetobacter baumannii ZAS1

Abhini

Rajan

Zuhara

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background This study targets the enhanced production of l-asparaginase, an antitumor enzyme by Acinetobacter baumannii ZAS1. This organism is an endophyte isolated from the medicinal plant Annona muricata. Plackett–Burman design (PBD) and central composite design (CCD) were used for statistical optimization of media components. Results The organism exhibited 18.85 ± 0.2 U/mL enzyme activities in unoptimized media. Eight variables: l-asparagine, peptone, glucose, lactose, yeast extract, NaCl, MgSO4, and Na2HPO4 were screened by PBD. Among them, only four factors—l-asparagine, peptone, glucose, and Na2HPO4—were found to affect enzyme production significantly (p < 0.05). Furthermore, the best possible concentrations and interactive effects of the components that enhance this enzyme's output were chosen by using CCD on these selected variables. The results revealed that an optimized medium produces a higher concentration of enzymes than the unoptimized medium. After optimizing media components, the maximum l-asparaginase activity was 45.59 ± 0.36 U/mL, around the anticipated value of 45.04 ± 0.42 U/mL. After optimization of process parameters, it showed a 2.41-fold increase in the production of l-asparaginase by the endophyte Acinetobacter baumannii ZAS1. Conclusion The findings of this study indicated that an endophyte, Acinetobacter baumannii ZAS1 that produces l-asparaginase could be used to increase enzyme output. However, using the statistical methods Plackett-Burman design and central composite design of response surface methodology is a handy tool for optimizing media components for increased l-asparaginase synthesis.

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“…The selected physicochemical properties namely peptone, casein, ammonium nitrate, beef extract, phenylalanine, yeast extract, urea, tyrosine, asparagine, glycine, valine, cysteine, methionine, glutamic acid, sucrose, starch, glucose, pH, and incubation time (day) were optimized using two factorial Plackett-Burman design to identify the significant variable tyrosinase production [24,25,39]. The nineteen variables were optimized by Plackett-Burman design.…”

Section: Bioprocess Optimization Of the Potent Fungal Isolate By Two-mentioning

confidence: 99%

Biochemical Properties of Tyrosinase from Aspergillus terreus and Penicillium copticola; Undecanoic Acid from Aspergillus flavus, an Endophyte of Moringa oleifera, Is a Novel Potent Tyrosinase Inhibitor

et al. 2021

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Tyrosinase is a copper-containing monooxygenase catalyzing the O-hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine then to dopaquinone that is profoundly involved in melanin synthesis in eukaryotes. Overactivation of tyrosinase is correlated with hyperpigmentation that is metabolically correlated with severe pathological disorders, so, inhibition of this enzyme is the most effective approach in controlling the overproduction of melanin and its hazardous effects. Thus, searching for a powerful, selective inhibitor of human tyrosinase to limit the hyper-synthesis of melanin is a challenge. Unlike the difficulty of overexpression of human tyrosinase, using fungal tyrosinase as a model enzyme to the human one to evaluate the mechanistics of enzyme inhibition in response to various compounds is the most feasible strategy. Thus, the purification of highly catalytic-efficient fungal tyrosinase, exploring a novel inhibitor, and evaluating the mechanistics of enzyme inhibition are the main objectives of this work. Aspergillus terreus and Penicillium copticola were reported as the most potential tyrosinase producers. The biochemical properties suggest that this enzyme displays a higher structural and catalytic proximity to human tyrosinase. Upon nutritional bioprocessing by Plackett–Burman design, the yield of tyrosinase was increased by about 7.5-folds, compared to the control. The purified tyrosinase was strongly inhibited by kojic acid and A. flavus DCM extracts with IC50 values of 15.1 and 12.6 µg/mL, respectively. From the spectroscopic analysis, the main anti-tyrosinase compounds of A. flavus extract was resolved, and verified as undecanoic acid. Further studies are ongoing to unravel the in vivo effect and cytotoxicity of this compound in fungi and human, that could be a novel drug to various diseases associated with hyperpigmentation by melanin.

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Process development for scale-up production of a therapeutic L-asparaginase by Streptomyces brollosae NEAE-115 from shake flasks to bioreactor

Cited by 34 publications

References 34 publications

Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

Response surface methodological optimization of l-asparaginase production from the medicinal plant endophyte Acinetobacter baumannii ZAS1

Biochemical Properties of Tyrosinase from Aspergillus terreus and Penicillium copticola; Undecanoic Acid from Aspergillus flavus, an Endophyte of Moringa oleifera, Is a Novel Potent Tyrosinase Inhibitor

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