Enhanced acetoin production by Serratia marcescens H32 using statistical optimization and a two-stage agitation speed control strategy

Sun, Jianan; Zhang, Liaoyuan; Ben, Rao; Han, Yunbin; Chu, Ju; Zhu, Junwen; Shen, Yang; Wei, Dongzhi

doi:10.1007/s12257-011-0587-4

Cited by 40 publications

(18 citation statements)

References 37 publications

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“…However, none of these strains had the ability to produce optically pure ( 3R )-AC or ( 3S )-AC. The current highest production of 75.2 g/l AC was achieved from Serratia marcescens H32 without considering its isomer (Sun et al 2012). Thus, S. marcescens was chosen to be the candidate to produce optically pure AC with high concentration in this study.…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Serratia marcescens MG1 for enhanced production of (3R)-acetoin

Dai

Bai

et al. 2016

Bioresour. Bioprocess.

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BackgroundOptically pure acetoin (AC) is an important platform chemical which has been widely used to synthesize novel optically active α-hydroxyketone derivatives and liquid crystal composites.ResultsIn this study, slaC and gldA encoding meso-2,3-butanediol dehydrogenase (meso-2,3-BDH) and glycerol dehydrogenase (GDH), respectively, in S. marcescens MG1 were knocked out to block the conversion from AC to 2,3-butanediol (2,3-BD). The resulting strain MG14 was found to produce a large amount of optically pure (3R)-AC with a little 2,3-BD, indicating that another enzyme responsible for 2,3-BD formation except meso-2,3-BDH and GDH existed in the strain MG1. Furthermore, SlaR protein, a transcriptional activator of AC cluster, was overexpressed using P C promoter in the strain MG14, leading to enhancement of the (3R)-AC yield by 29.91%. The recombinant strain with overexpression of SlaR, designated as S. marcescens MG15, was used to perform medium optimization for improving (3R)-AC production.ConclusionUnder the optimized conditions, 39.91 ± 1.35 g/l (3R)-AC was produced by strain MG15 with the productivity of 1.11 g/l h and the conversion rate of 80.13%.

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Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Serratia marcescens MG1 for enhanced production of (3R)-acetoin

Dai

Bai

et al. 2016

Bioresour. Bioprocess.

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“…Acetoin (3‐hydroxy‐2‐butanone, AC) is a natural flavor commonly used in wine, buffer, honey, garnet berry and strawberry as a food additive . It has also been widely applied in cosmetics, pharmaceuticals and chemical synthesis .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, optically pure AC is widely used to synthesize novel optically active α‐hydroxyketone derivatives and liquid crystal composites . Some microbial fermentation processes have been developed to enhance racemic AC production in recent years . However, until now, a native microorganism with the ability to produce a single configuration of optically pure (3 R )‐AC or (3 S )‐AC from glucose has not been found.…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering ofEscherichia colifor efficient production of (3R)-acetoin

Xie

et al. 2014

J. Chem. Technol. Biotechnol.

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BACKGROUND: Optically pure acetoin is an important potential pharmaceutical intermediate. It has also been widely used to synthesize novel optically active α-hydroxyketone derivatives and liquid crystal composites. Recombinant Escherichia coli was developed for efficient (3R)-acetoin production. Culture medium optimization and process control were carried out to improve (3R)-acetoin yield by the engineered strain. RESULTS: A synthetic pathway involved the budRAB genes from Serratia marcescens and NADH oxidase gene fromLactobacillus brevis in E. coli was developed for efficient (3R)-acetoin production. Batch culture showed that 23.4 g L −1 of (3R)-acetoin could be obtained from 60 g L −1 glucose by the engineered strain. Chiral-column GC analysis indicated that the stereoisomeric purity of (3R)-acetoin produced was 97.3%. Further, the medium composition was optimized in shake flasks by an orthogonal design method. Under optimal conditions, (3R)-acetoin concentration reached 38.3 g L −1 in flask fermentation. Fed-batch fermentation based on a suitable agitation speed was carried out in a 5 L bioreactor, and maximum (3R)-acetoin concentration of 60.3 g L −1 was achieved with a productivity of 1.55 g L −1 h −1 and yield 86.3%. CONCLUSION: An engineering E. coli for efficient (3R)-acetoin production was constructed. The optimization of fermentation variables and fed-batch culture resulted in a maximum (3R)-acetoin concentration of 60.3 g L −1 . DISCUSSIONChiral AC has recently been paid increasing attention due to its potential industrial and pharmaceutical applications. 7 However, natural microorganisms usually produce a mixture of (3R)-AC and (3S)-AC, which is difficult to accumulate due to a large J Chem Technol Biotechnol 2015; 90: 93-100

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“…New findings have also proved that the fermentation duration can be shortened effectively and acetoin production can be improved by changing the agitation speed to control the dissolved oxygen levels [23], [27]. However, there was still considerable amount of byproduct 2,3-butanediol through these above efforts.…”

Section: Introductionmentioning

confidence: 99%

Two-Stage pH Control Strategy Based on the pH Preference of Acetoin Reductase Regulates Acetoin and 2,3-Butanediol Distribution in Bacillus subtilis

et al. 2014

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Acetoin reductase/2,3-butanediol dehydrogenase (AR/BDH), which catalyzes the interconversion between acetoin and 2,3-butanediol, plays an important role in distribution of the products pools. This work characterized the Bacillus subtilis AR/BDH for the first time. The enzyme showed very different pH preferences of pH 6.5 for reduction and pH 8.5 for oxidation. Based on these above results, a two-stage pH control strategy was optimized for acetoin production, in which the pH was controlled at 6.5 for quickly converting glucose to acetoin and 2,3-butanediol, and then 8.0 for reversely transforming 2,3-butanediol to acetoin. By over-expression of AR/BDH in the wild-type B. subtilis JNA 3-10 and applying fed-batch fermentation based on the two-stage pH control strategy, acetoin yield of B. subtilis was improved to a new record of 73.6 g/l, with the productivity of 0.77 g/(l·h). The molar yield of acetoin was improved from 57.5% to 83.5% and the ratio of acetoin/2,3-butanediol was switched from 2.7∶1 to 18.0∶1.

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Enhanced acetoin production by Serratia marcescens H32 using statistical optimization and a two-stage agitation speed control strategy

Cited by 40 publications

References 37 publications

Metabolic engineering of Serratia marcescens MG1 for enhanced production of (3R)-acetoin

Metabolic engineering of Serratia marcescens MG1 for enhanced production of (3R)-acetoin

Metabolic engineering ofEscherichia colifor efficient production of (3R)-acetoin

Two-Stage pH Control Strategy Based on the pH Preference of Acetoin Reductase Regulates Acetoin and 2,3-Butanediol Distribution in Bacillus subtilis

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