Optimization of Culture Conditions for Production of the Anti-Leukemic Glutaminase Free L-Asparaginase by Newly IsolatedStreptomyces olivaceusNEAE-119 Using Response Surface Methodology

Abstract

Among the antitumor drugs, bacterial enzyme L-asparaginase has been employed as the most effective chemotherapeutic agent in pediatric oncotherapy especially for acute lymphoblastic leukemia. Glutaminase free L-asparaginase producing actinomycetes were isolated from soil samples collected from Egypt. Among them, a potential culture, strain NEAE-119, was selected and identified on the basis of morphological, cultural, physiological, and biochemical properties together with 16S rRNA sequence as Streptomyces olivaceus NEAE-119 and sequencing product (1509 bp) was deposited in the GenBank database under accession number KJ200342. The optimization of different process parameters for L-asparaginase production by Streptomyces olivaceus NEAE-119 using Plackett-Burman experimental design and response surface methodology was carried out. Fifteen variables (temperature, pH, incubation time, inoculum size, inoculum age, agitation speed, dextrose, starch, L-asparagine, KNO3, yeast extract, K2HPO4, MgSO4·7H2O, NaCl, and FeSO4·7H2O) were screened using Plackett-Burman experimental design. The most positive significant independent variables affecting enzyme production (temperature, inoculum age, and agitation speed) were further optimized by the face-centered central composite design-response surface methodology.

Optimization of culture conditions for penicilazaphilone C production by a marine-derived fungus Penicillium sclerotiorum M-22

“…Fermentation time, initial pH and concentration of nutritional ingredients play significant roles in the fungal fermentation, as these have been reported to influence production of natural products by other micro‐organisms (El‐Naggar Nel et al . ; Li et al . ).…”

Modeling-based optimization approaches for the development of Anti- Agrobacterium tumefaciens activity using Streptomyces sp TN71

“…Secondary metabolites production in actinomycetes is often stimulated by slowly-assirnilated complex carbohydrates such as soluble starch, but is suppressed by rapidly-utilized carbon sources such as presence of glucose [32]. In fact, high concentration usually inhibits the biosynth esis of many antibiotics in Streptomycetes [33][34][35][36]. A possible ex planation of this phenomenon is that glucose may cause catabolic re pression, in which the production of enzymes for secondary metabolites biosynthesis might be inhibited [32,37].…”

Influence of glucose and stirring in the fermentation process in order to produce anti- Candida metabolites produced by Streptomyces sp.

“…The nature and concentration of nutrients in the medium such as carbon, nitrogen, phosphorus and minerals as well as the essential substances for biosynthetic pathway can promote the production of larger quantities of one or another compound inferring directly on its performance (Gupte, Kulkarni, 2002;Chen et al, 2012;El-Naggar et al, 2015).…”

“…Among the external factors with influence at the biosynthesis of secondary metabolites by microorganisms, the sources of carbon and nitrogen are highly relevant, since they are related to both substrate availability for the synthesis of metabolites as to the modulation of the enzymatic process and may activate and stabilize the enzymes involved in the process (Gupte, Kulkarni, 2002;El-Naggar et al, 2015).…”

“…However, the production of some metabolites is suppressed by the inhibition of any enzyme involved in the process and consequently leads to activation of other metabolic pathways (El-Naggar et al, 2015;Sanchez, Quintero, Ochoa, 2015).…”