Optimization for the enhanced production of avermectin B1b from Streptomyces avermitilis DSM 41445 using artificial neural network

Siddique, Samia; Nelofer, Rubina; Syed, Quratulain; Adnan, Ahmad; Qureshi, Fahim Ashraf

doi:10.1007/s13765-014-4194-x

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…Due to the medicinal value and the clinical importance described above, related researches on amphotericin B and its derivatives are more in-depth and mature. Concurrently, many classical breeding methods of high-yield strains including fermentation development (Siddique et al, 2014 ; Ahsan et al, 2017 ; Ju et al, 2017 ; Zhao et al, 2017 ) and efficient bioprocesses (Santos-Aberturas et al, 2011 ; Yao et al, 2018 ) have been applied to increase the titer of several polyene macrolide antibiotics (Pereira et al, 2008 ; Zhang et al, 2017 ). Another important strategy was reported, such that short-chain fatty acid, lower alcohols, and some salt substances can be added as precursors of macrolide antibiotics to derive a high product titer (Jing et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Enhanced AmB Production in Streptomyces nodosus by Fermentation Regulation and Rational Combined Feeding Strategy

Zhang

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Amphotericin B is a clinically important polyene macrolide antibiotic with a broad-spectrum antifungal activity. In this work, the addition of key precursors and differential metabolites, combined with staged fermentation process control strategies, was carried out to improve AmB production. Rationally designed addition strategies were proposed as follows: 4 mg/L isopropanol, 1 mM alanine, 1 g/L pyruvate, and 0.025 g/L nicotinamide were supplemented at 24 h. The AmB titer was ultimately enhanced to 6.63 g/L, with 28.5% increase in shake flasks fermentation. To further promote the biosynthesis of AmB, different glucose feeding strategies were investigated and the highest AmB titer (15.78 g/L) was obtained by constant speed fed-batch fermentation in a 5-L fermentor. Subsequently, compared with the batch fermentation (9.89 g/L), a novel combined feeding strategy was ultimately developed to improve the production of AmB by 85.9%, reaching 18.39 g/L that is the highest titer of AmB ever reported so far, in which the optimized components were fed at 24 h and the staged fermentation regulation strategies were used simultaneously. Moreover, the ratio of co-metabolite AmA decreased by 32.3%, from 3.1 to 2.1%. Through the detection of extracellular organic acids, the changes in α-ketoglutaric acid, pyruvate, and citric acid concentrations were identified as the most flexible metabolite nodes to further clarify the potential mechanism under different fermentation regulation strategies. These results demonstrated that the strategies above may provide new guidance for the industrial-scale production of AmB.

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Section: Introductionmentioning

confidence: 99%

Enhanced AmB Production in Streptomyces nodosus by Fermentation Regulation and Rational Combined Feeding Strategy

Zhang

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Enhanced avermectin production by Streptomyces avermitilis ATCC 31267 using high-throughput screening aided by fluorescence-activated cell sorting

Cao

Luo

Zeng

et al. 2017

Appl Microbiol Biotechnol

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Avermectins, produced by Streptomyces avermitilis, are important antiparasitic agents. The use of traditional microbial breeding methods for this organism has been limited by the low-throughput shake flask-based screening process. The unique growth cycle of actinomycetes makes the establishment of a reliable high-throughput screening (HTS) process difficult. To enhance the efficiency of screening strains with high yields of avermectin, a HTS process aided by fluorescence-activated cell sorting (FACS) was established. Four different spore solutions were investigated for maintaining a relatively high viability of spores. Propidium iodide (PI) and fluorescein diacetate (FDA) were used to discriminate between dead and live spores using the FACS system. Spores stained with 7-μg/mL PI and 15-μg/mL FDA at 4 °C in the dark for 30 min resulted in optimum sorting. Spores were treated by atmospheric and room temperature plasma (ARTP). Single live spores were sorted and sprayed into 96-well microtiter plates containing 50 μL of solid agar culture medium. Solid-liquid combinatorial microculture was used for high-throughput avermectin culture. A high-titer avermectin producer (G9) was obtained from 5760 mutants after mutagenesis and HTS. Compared with the original strain, the titer was improved by 18.9% on flask culture and 20.6% on fermenter, respectively. The HTS process established in this study could easily be transferred to other similar target products produced by actinomycetes.

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Optimization for the enhanced production of avermectin B1b from Streptomyces avermitilis DSM 41445 using artificial neural network

Cited by 2 publications

References 23 publications

Enhanced AmB Production in Streptomyces nodosus by Fermentation Regulation and Rational Combined Feeding Strategy

Enhanced AmB Production in Streptomyces nodosus by Fermentation Regulation and Rational Combined Feeding Strategy

Enhanced avermectin production by Streptomyces avermitilis ATCC 31267 using high-throughput screening aided by fluorescence-activated cell sorting

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