Scale-up fermentation of echinocandin type antibiotic FR901379

Kanda, Munekazu; Yamamoto, Eiji; Hayashi, Akiyo; Yabutani, Tomoki; Yamashita, Michio; Honda, Hiroyuki

doi:10.1016/j.jbiosc.2009.07.019

Cited by 17 publications

(10 citation statements)

References 11 publications

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“…Many of them have reported that the impeller types and combinations have an obviously correlation with the volumetric oxygen transfer coefficient. Homogeneous mixing, moderate shear environment and higher product production could be achieved through optimizing impeller number, types and combinations [ 42 , 43 , 44 , 45 , 46 ]. Hence, in order to improve the flow field and air distribution inside the fermentor, and further increase glycoprotein GP-1 production, different impeller combinations in large-scale fermentor will be optimized by using CFD technique as future work.…”

Section: Discussionmentioning

confidence: 99%

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient

et al. 2018

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The effects of temperature, agitation and aeration on glycoprotein GP-1 production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were systematically investigated. The maximum final GP-1 production was achieved at an agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of 30 °C. By using a dynamic gassing out method, the effects of agitation and aeration on volumetric oxygen transfer coefficient (kLa) were also studied. The values of volumetric oxygen transfer coefficient in the logarithmic phase increased with increase of agitation speed (from 14.53 to 32.82 h−1) and aeration rate (from 13.21 to 22.43 h−1). In addition, a successful scale-up from bench-scale to pilot-scale was performed based on volumetric oxygen transfer coefficient, resulting in final GP-1 production of 3.92, 4.03, 3.82 and 4.20 mg/L in 5 L, 15 L, 70 L and 500 L fermentors, respectively. These results indicated that constant volumetric oxygen transfer coefficient was appropriate for the scale-up of batch fermentation of glycoprotein GP-1 by Streptomyces kanasenisi ZX01, and this scale-up strategy successfully achieved 100-fold scale-up from bench-scale to pilot-scale fermentor.

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Section: Discussionmentioning

confidence: 99%

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient

et al. 2018

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“…A fed-batch fermentation process may relieve the above problem by controlling the substrate concentration below the inhibitory levels (Dolejs et al 2014;Le Meur et al 2014). Previous studies showed that the fed-batch strategy was effective to increase the productivity of echinocandins (Kanda et al 2010). In this study, to explore the potential of ECB production, the two-stage temperature control strategy was further investigated to improve ECB productivity by combining different mannitol feeding modes.…”

Section: Further Improvement Of Ecb Production By a Combined Fed-batch Strategymentioning

confidence: 99%

“…Owing to the low toxicity, broad antifungal activity, and excellent pharmacokinetic properties of the echinocandin-type drug, their production by microbial fermentation has been a focus of much attention (Balkovec et al 2014;Zou et al 2015a). Many reports are available on echinocandin fermentation (Cockshott and Hartman 2001;Kanda et al 2009Kanda et al , 2010Bills et al 2008;Pollard et al 2007;Hu et al 2016). However, the ECB production by microbial fermentation continues to suffer challenges, such as high viscosity of fermentation, long fermentation periods and low ECB productivity.…”

Section: Introductionmentioning

confidence: 99%

Integrated strategy of temperature shift and mannitol feeding for enhanced production of echinocandin B by Aspergillus nidulans CCTCC M2012300

et al. 2019

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The production of echinocandin B (ECB) by Aspergillus nidulans CCTCC M2012300 was improved by integrating the temperature-shift and fed-batch control strategies. The kinetic characteristics of batch cultures were analyzed at different culture temperatures, and then a two-stage temperature control strategy was established. In the first 6 days, the temperature was maintained at 30 °C to obtain the maximal cell growth rate; subsequently, 25 °C was used to gain a high ECB formation rate. On the basis of temperature control, the ECB productivity was increased to 143.3 mg/(L day), which was a 1.3-fold improvement compared with the optimal constant-temperature cultivations. The influences of fed-batch cultures were further investigated. A maximal ECB productivity of 170.8 mg/(L day) was obtained through a three-stage mannitol pulse-feeding strategy, which was another 1.2-fold improvement than that of the batch fermentation. This is the first report of the use of a two-stage temperature control fed-batch strategy in ECB fermentation. This strategy was simple and economical to operate and may provide new guidance for the industrial-scale production of ECB.

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“…It is well known that the cultivation conditions, including chemical and physical parameters, would change the morphology of actinomyces, and further affect their antibiotic productivity (Chen et al 1999;Dobson et al 2008;El-Sabbagh et al 2006;Kanda et al 2010). For example, a relationship between morphology and productivity of antibiotics by Streptomyces has been found, including with regard to the composition, structure, hydrophobicity or charge of the cell wall, as well as the presence of extracellular polymeric substances (Choi et al 1998;Jonsbu et al 2002;Pinto et al 2004;Tamura et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Using the mycelium-covered cereals as an efficient inoculation method for rapamycin fermentation in a 15-L fermenter using Streptomyces hygroscopicus

Yen

Chiang

2015

Bioresour. Bioprocess.

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Background: Rapamycin is produced from Streptomyces hygroscopicus, and was initially identified as an antifungal antibiotic. More recently, rapamycin has been found to have various medical applications, including in relation to immunosuppression and anti-aging. Due to its complex structure, biological production is the major route for commercialized rapamycin production. The conventional fermentation process requires a large seed fermenter for the inoculation process (in general, the volume of the seed fermenter is equal to 5-10 % that of the production fermenter), which presents challenges with regard to scaling up production, due to the high investment costs of seed fermenters. This study explored different inoculation strategies for rapamycin production in a 15-L agitation fermenter. Results:The results indicated that solid-state fermentation (SSF) using barley as the substrate is a suitable method for the inoculation. The highest rapamycin concentration measured in the batch with SSF (barley) inoculated was about 520 mg/L, which was significantly higher than that of 400 mg/L obtained in the batch inoculated with 5 % liquid seed medium. Besides the higher rapamycin production, using SSF of barley as the inoculation method can greatly reduce both the labor and cost requirements. Conclusions:The usage of mycelium-covered barley as the solid substrate for the inoculation of 15-L fermenter leading to a higher rapamycin production compared to that of conventional liquid seed medium. The solid-state inoculation method can avoid both the intensive labor requirement and costly seed fermenter needed with the latter approach. This inoculation method thus has the potential to be applied to the large-scale production of rapamycin.

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Scale-up fermentation of echinocandin type antibiotic FR901379

Cited by 17 publications

References 11 publications

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient

Integrated strategy of temperature shift and mannitol feeding for enhanced production of echinocandin B by Aspergillus nidulans CCTCC M2012300

Using the mycelium-covered cereals as an efficient inoculation method for rapamycin fermentation in a 15-L fermenter using Streptomyces hygroscopicus

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