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

Lv, Xin; Dai, Lu; Bai, Fangmin; Wang, Zhanqing; Zhang, Liaoyuan; Shen, Yang

doi:10.1186/s40643-016-0128-2

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…Acetoin exists as ( R )- and ( S )- stereoisomers, both of which are potential drug intermediates. Optically pure acetoin has been widely used as the precursor for synthesizing novel optically active materials, including liquid crystal composites and α-hydroxyketone derivatives ( Xin et al, 2016 , Xu et al, 2015 ). ( R )-acetoin is a female sex pheromone of Amphimallon solstitiale (L.), which attracts swarming males, whereas racemic acetoin was non-functional in this respect ( Tolasch et al, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous biosynthesis of (R)-acetoin and ethylene glycol from D-xylose through in vitro metabolic engineering

Jia

Kelly

Han

2018

Metabolic Engineering Communications

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(R)-acetoin is a four-carbon platform compound used as the precursor for synthesizing novel optically active materials. Ethylene glycol (EG) is a large-volume two-carbon commodity chemical used as the anti-freezing agent and building-block molecule for various polymers. Currently established microbial fermentation processes for converting monosaccharides to either (R)-acetoin or EG are plagued by the formation of undesirable by-products. We show here that a cell-free bioreaction scheme can generate enantiomerically pure acetoin and EG as co-products from biomass-derived D-xylose. The seven-step, ATP-free system included in situ cofactor regeneration and recruited enzymes from Escherichia coli W3110, Bacillus subtilis shaijiu 32 and Caulobacter crescentus CB 2. Optimized in vitro biocatalytic conditions generated 3.2 mM (R)-acetoin with stereoisomeric purity of 99.5% from 10 mM D-xylose at 30 °C and pH 7.5 after 24 h, with an initial (R)-acetoin productivity of 1.0 mM/h. Concomitantly, EG was produced at 5.5 mM, with an initial productivity of 1.7 mM/h. This in vitro biocatalytic platform illustrates the potential for production of multiple value-added biomolecules from biomass-based sugars with no ATP requirement.

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Section: Introductionmentioning

confidence: 99%

Simultaneous biosynthesis of (R)-acetoin and ethylene glycol from D-xylose through in vitro metabolic engineering

Jia

Kelly

Han

2018

Metabolic Engineering Communications

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“…Glycerol can be a carbon source for the biosynthesis of organic acids. Lv et al knocked out gld A encoding glycerol dehydrogenase in an engineered acetoin-producing strain, Serratia marcescens, to reduce the synthesis of by-products downstream of glycerol [ 33 ]. Hao et al realized the reduction of succinate by 37.4% by knocking out fumarate reductase frdB [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Metabolic Engineering of Escherichia coli for High-Level Production of (R)-Acetoin from Low-Cost Raw Materials

Diao

Chen

et al. 2023

Microorganisms

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Acetoin is an important four-carbon platform chemical with versatile applications. Optically pure (R)-acetoin is more valuable than the racemate as it can be applied in the asymmetric synthesis of optically active α-hydroxy ketone derivatives, pharmaceuticals, and liquid crystal composites. As a cytotoxic solvent, acetoin at high concentrations severely limits culture performance and impedes the acetoin yield of cell factories. In this study, putative genes that may improve the resistance to acetoin for Escherichia coli were screened. To obtain a high-producing strain, the identified acetoin-resistance gene was overexpressed, and the synthetic pathway of (R)-acetoin was strengthened by optimizing the copy number of the key genes. The engineered E. coli strain GXASR-49RSF produced 81.62 g/L (R)-acetoin with an enantiomeric purity of 96.5% in the fed-batch fermentation using non-food raw materials in a 3-L fermenter. Combining the systematic approach developed in this study with the use of low-cost feedstock showed great potential for (R)-acetoin production via this cost-effective biotechnological process.

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“…Bacteria with alsSD operons produce 3R-AC via acetolactate decarboxylation; therefore, theoretically only the knockout of multiple BDHs in wild strains is necessary to achieve high optical purity in 3R-AC. For instance, Lv et al knocked out the meso-BDH and GDH-encoding genes slaC and gidA in S. marcescens MG1 and prevented the conversion of AC to BD, obtaining strains with the ability to accumulate large amounts of 3R-AC [ 59 ]. Wang et al eliminated the budC gene encoding meso-BDH in K. pneumoniae CGMCC 1.6366 and obtained 3R-AC with a 96.0% optical purity [ 60 ].…”

Section: Production Of Optically Pure Ac/bdmentioning

confidence: 99%

Mechanism of microbial production of acetoin and 2,3-butanediol optical isomers and substrate specificity of butanediol dehydrogenase

Li,

Zhao,

Yao

et al. 2023

Microb Cell Fact

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Abstract3-Hydroxybutanone (Acetoin, AC) and 2,3-butanediol (BD) are two essential four-carbon platform compounds with numerous pharmaceutical and chemical synthesis applications. AC and BD have two and three stereoisomers, respectively, while the application of the single isomer product in chemical synthesis is superior. AC and BD are glucose overflow metabolites produced by biological fermentation from a variety of microorganisms. However, the AC or BD produced by microorganisms using glucose is typically a mixture of various stereoisomers. This was discovered to be due to the simultaneous presence of multiple butanediol dehydrogenases (BDHs) in microorganisms, and AC and BD can be interconverted under BDH catalysis. In this paper, beginning with the synthesis pathways of microbial AC and BD, we review in detail the studies on the formation mechanisms of different stereoisomers of AC and BD, summarize the properties of different types of BDH that have been tabulated, and analyze the structural characteristics and affinities of different types of BDH by comparing them using literature and biological database data. Using microorganisms, recent research on the production of optically pure AC or BD was also reviewed. Limiting factors and possible solutions for chiral AC and BD production are discussed.

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

Cited by 9 publications

References 26 publications

Simultaneous biosynthesis of (R)-acetoin and ethylene glycol from D-xylose through in vitro metabolic engineering

Simultaneous biosynthesis of (R)-acetoin and ethylene glycol from D-xylose through in vitro metabolic engineering

Metabolic Engineering of Escherichia coli for High-Level Production of (R)-Acetoin from Low-Cost Raw Materials

Mechanism of microbial production of acetoin and 2,3-butanediol optical isomers and substrate specificity of butanediol dehydrogenase

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