Development of Fed-Batch Cultivation Strategy for Efficient Oxytetracycline Production by Streptomyces rimosus at Semi-Industrial Scale

Elsayed, Elsayed Ahmed; Omar, Hoda; El‐Enshasy, Hesham Ali

doi:10.1590/s1516-89132015050184

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…The possible solution of this problem is a fed-batch fermentation, since the concentration of the limiting substrate may be maintained at a very low level avoiding repressive effects of high substrate concentration and improving the final antibiotic yield (Callewaert and de Vuyst 2000; Elsayed et al 2015). Taking into account this fact, a continuous addition of 50% sterile sucrose solution was provided after 48 h of fermentation under controlled optimal pH and DO concentration (6.8–7.0 and 50%, respectively).…”

Section: Resultsmentioning

confidence: 99%

Scaling up a virginiamycin production by a high-yield Streptomyces virginiae VKM Ac-2738D strain using adsorbing resin addition and fed-batch fermentation under controlled conditions

Dzhavakhiya¹,

Savushkin²,

Ovchinnikov³

et al. 2016

3 Biotech

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Virginiamycin produced by Streptomyces virginiae as a natural mix of macrocyclic peptidolactones M and S is widely used in the industrial production of ethanol fuel and as an antibiotic feed additive for cattle and poultry. Its main antimicrobial components, M1 and S1 factors, act synergistically if the M1:S1 ratio in the final product is 70–75:25–30. This fact significantly complicates the development of stable high-yield strains suitable for industrial application. In the previous work, authors obtained a mutant S. virginiae VKM Ac-2738D strain, characterized by a high productivity in flasks and the optimum M1:S1 ratio (75:25) in the final product. In this study, the scale-up of the virginiamycin production by VKM AC-2738D from shake flasks to a pilot-scale (100 L) stirred fermentor was carried out and the possibility of the in situ use of synthetic adsorbing resins to remove virginiamycin from culture broth was assessed. After the optimization of pH and dissolved oxygen concentration (6.8–7.0 and 50%, respectively), the fed-batch fermentation of VKM Ac-2738D with continuous addition of 50% sucrose solution (5 g/L/day starting from 48 h of fermentation) resulted in a final virginiamycin titer of 4.9 g/L. Among four tested resins, Diaion® HP21 added to fermentation medium prior to sterilization absorbed 98.5% of the total virginiamycin that simplifies its further recovery procedure and increased its total titer to 5.6 g/L at the M1:S1 ratio of 74:26. The developed technology has several important advantages, which include (1) the optimum M1:S1 ratio in the final product, (2) the possibility to use sucrose as a carbon source instead of traditionally used and more expensive glucose or d-maltose, and (3) selective binding of up to 98.5% of produced virginiamycin on the adsorbing resin.

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Section: Resultsmentioning

confidence: 99%

Scaling up a virginiamycin production by a high-yield Streptomyces virginiae VKM Ac-2738D strain using adsorbing resin addition and fed-batch fermentation under controlled conditions

Dzhavakhiya¹,

Savushkin²,

Ovchinnikov³

et al. 2016

3 Biotech

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“…and fermentation modes (batch, substrate fed-batch, whole nutrient fed-batch, etc.) 51 , 75 , 76 . Carbon catabolite repression the biosynthesis of many bioactive metabolites is a big problem caused by the carbon source (sucrose) during the Streptomyces virginiae cultivation.…”

Section: Discussionmentioning

confidence: 99%

“…The filtrates were then evaporated using a rotary evaporator at 40 °C. The crude intracellular bioactive metabolite was extracted from the washed biomass (the pellet) that treated with CTAB extraction buffer (100 mM Tris-Cl (pH 8.0), 20 mM EDTA (pH 8.0), 1.4 M NaCl, 2% (w/v) cetyltrimethyl ammonium bromide and 1% PVP 40,000 (polyvinyl pyrrolidone) for 2 hr under shaking condition and finally centrifuged at 14000 rpm for 10 min 44 , 50 , 51 . The concentrated bioactive metabolites extracts were then transferred into clean glass screw cap tube and stored at 4 °C for further use.…”

Section: Methodsmentioning

confidence: 99%

“…In an accurate industrial bioprocesses strategy, living microbial cells used as cell factories that produce bioactive metabolites by utilizing mathematical kinetic models which are able to develop these cell properties and/or the final production bioprocesses 23 – 25 , 46 , 51 , 55 . Kinetic cell factory modeling used to understand, predict, develop and assess the effects of modifying (adding and/or removing) cell cultivation components and/or cultivation conditions 23 – 25 , 44 .…”

Section: Methodsmentioning

confidence: 99%

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Bioprocessing strategies for cost-effective large-scale biogenic synthesis of nano-MgO from endophytic Streptomyces coelicolor strain E72 as an anti-multidrug-resistant pathogens agent

EL-Moslamy

2018

Sci Rep

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In this report, the local nano-MgO synthesizer strain has been isolated from Ocimum sanctum plant and deposited in GenBank as endophytic Streptomyces coelicolor strain E72. Its intracellular metabolic fraction that contains 7.2 μg/μl of carbohydrate, 6.3 g/l of protein and 5.2 nmol/hr/ml of nitrate reductase used to produce multi-surface shaped nano-MgO with diameter ~25 nm. To the best of our knowledge, this is the first report using statistical nanobiotechnological strategies (Plackett -Burman, Box-Behnken and Taguchi experimental designs) to study and evaluate the endophytic S. coelicolor biomass production (123.3 g/l) and extract the highest bioactive metabolites that used for biogenic synthesis of nano-MgO (320 g/l) through exponential sucrose pulses feeding fermentation strategy after 192 hr in semi industrial scale bioreactor (7 L). Purified nano-MgO applied in vitro against multi-drug resistant human pathogens and the large inhibition zone recorded against Shigella flexneri (108 ± 10.53 mm). The average of MICs was recorded as 25 µg/ml that inhibited 90% of the pathogenic living cells and compared with 100 mg/ml ampicilin/sulbactam solution that killed 40% of the same pathogen. These results are expected to gather sufficient knowledge to discover and develop a new cheap and eco-friendly nano-MgO as an extremely strong antimicrobial agent used in biomedical applications.

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“…Considering that OTC is medically important antibiotic, and it is produced at large scale by the industrial fermentation processes, most of the studies in the past have been focused predominantly on cultivation conditions which are comparable or even identical to the cultivation conditions used in industrial environment (Singh et al 2012;Elsayed et al 2015). In our study, however, we took different approach.…”

Section: Rima1a2 a Distinctive Two-component System In S Rimosus M4018mentioning

confidence: 99%

Study on a two-component signal transduction system RimA1A2 that negatively regulates oxytetracycline biosynthesis in Streptomyces rimosus M4018

Xiong

Mohsin

et al. 2019

Bioresour. Bioprocess.

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Biosynthesis of secondary metabolites in actinobacteria is regulated by complex regulatory mechanisms on responding environmental changes. In this study, we have identified a two-component system (TCS) designated as RimA1A2 in the genome of Streptomyces rimosus M4018, with high homology to the TCS RapA1A2 from Streptomyces coelicolor, known for its positive regulatory function towards actinorhodin (ACT) biosynthesis. Using RT-PCR analysis, we demonstrate that rimA1 encodes response regulator (RR) and rimA2 encoding histidine kinase (HK) from S. rimosus that are co-transcribed as a single-polycistronic mRNA. When S. rimosus was cultivated on standard media, no significant difference in culture growth or morphological properties was observed between the rimA1-disrupted mutant and parent strain M4018. However, the rimA1-disrupted strain displayed significant increase in oxytetracycline (OTC) titer when cultivated in minimal medium (MM) containing glycine as sole nitrogen source, and the transcription of selected genes involved in OTC biosynthesis was increased, supporting the hypothesis that RimA1A2 has a negative regulatory role in OTC biosynthesis via global regulation. We observed an increased resistance of the rimA1-disrupted mutant strain to selected antibiotics. Interestingly, in the rimA1-disrupted strain, OTC biosynthesis was affected under different environmental stress conditions such as osmotic and oxidative stress. Accordingly, this phenotype was observed in a medium-dependent manner. Considering complexity of regulatory networks in antibiotic-producing organisms, this study demonstrates the importance of cultivation conditions, which is often neglected. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Development of Fed-Batch Cultivation Strategy for Efficient Oxytetracycline Production by Streptomyces rimosus at Semi-Industrial Scale

Abstract: Oxytetracycline (OTC) production by Streptomyces rimosus was studied in batch and fed-batch cultures in

Cited by 17 publications

References 29 publications

Scaling up a virginiamycin production by a high-yield Streptomyces virginiae VKM Ac-2738D strain using adsorbing resin addition and fed-batch fermentation under controlled conditions

Scaling up a virginiamycin production by a high-yield Streptomyces virginiae VKM Ac-2738D strain using adsorbing resin addition and fed-batch fermentation under controlled conditions

Bioprocessing strategies for cost-effective large-scale biogenic synthesis of nano-MgO from endophytic Streptomyces coelicolor strain E72 as an anti-multidrug-resistant pathogens agent

Study on a two-component signal transduction system RimA1A2 that negatively regulates oxytetracycline biosynthesis in Streptomyces rimosus M4018

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