Biotechnological production of chiral acetoin

Recent advances in biotechnology have enabled the production of a variety of high-value compounds such as chiral acetoin (AC) by environmentally friendly biological methods. Microbial fermentation routes based on natural, engineered, or heterologous hosts are being used to enhance the production performance of chiral AC, including titer, yield, and productivity. Biocatalysis approaches using natural or artificial enzymatic reaction cascades have been applied to improve the optical purity of chiral AC and to explore the feasibility of chiral AC production from cheap and renewable resources. Progress in obtaining high-yield and high-tolerance strains, discovering more efficient enzymes, and designing more streamlined pathways may create breakthroughs for chiral AC biosynthesis. Acetoin (AC) is an important platform bulk chemical with versatile applications. It exists in two stereoisomeric forms: (3R)-AC and (3S)-AC. Both stereoisomers could be potentially applied in the pharmaceutical industry, agriculture, and in optically active α-hydroxyketone derivative synthesis. Chiral AC production has recently become a new research focus in biotechnology. Fermentative and biocatalytic routes that can produce (3R)-AC or (3S)-AC with high optical purity have been developed over the past several years. In this review we summarize recent advances in strain screening, metabolic engineering, and biocatalytic system construction aimed at improving the production of chiral AC. Limiting factors and possible solutions for chiral AC production are discussed. Acetoin (AC) is an important platform bulk chemical with versatile applications. It exists in two stereoisomeric forms: (3R)-AC and (3S)-AC. Both stereoisomers could be potentially applied in the pharmaceutical industry, agriculture, and in optically active α-hydroxyketone derivative synthesis. Chiral AC production has recently become a new research focus in biotechnology. Fermentative and biocatalytic routes that can produce (3R)-AC or (3S)-AC with high optical purity have been developed over the past several years. In this review we summarize recent advances in strain screening, metabolic engineering, and biocatalytic system construction aimed at improving the production of chiral AC. Limiting factors and possible solutions for chiral AC production are discussed. a valuable compound that is widely used in the food, chemical and pharmaceutical industries. Given its various applications and potential for bulk production, AC is one of the top 30 platform chemicals whose development and utilization are given priority by the US Department of Energy. the precursor to both (3R)-AC and (3S)-AC in bacterial metabolism that is produced by the condensation of pyruvate. It can be converted to (3R)-AC through α-acetolactate decarboxylase or non-enzymatic decarboxylation, and to diacetyl through non-enzymatic oxidative decarboxylation (NOD). an enzyme that catalyzes the generation of (3R)-AC from α-acetolactate. It is also called AlsD or BudA in some microorganisms. an enzyme that catalyzes the production of α-acetolactate from pyruvate. It is also called AlsS or BudB in some microorganisms. the reduction product of AC. It exists in three isomers, namely (2R,3R)-2,3-BD, (2S,3S)-2,3-BD, and meso-2,3-BD. (2R,3R)-2,3-BD and meso-2,3-BD can be produced through microbial fermentation. (2R,3R)-2,3-BD can be used to produce (3R)-AC via (R)-specific dehydrogenation, while meso-2,3-BD can be used to generate (3R)-AC or (3S)-AC by (S)-specific or (R)-specific dehydrogenation, respectively. an (R)-specific secondary alcohol dehydrogenase that catalyzes the production of (2R,3R)-2,3-BD from (3R)-AC, meso-2,3-BD production from (3S)-AC, and (3R)-AC production from diacetyl. It can be used to catalyze the specific dehydrogenation of the (R)-hydroxyl group in meso-2,3-BD and (2R,3R)-2,3-BD to produce (3S)-AC and (3R)-AC, respectively. the natural precursor of (3S)-AC in bacterial metabolism, which can be produced by non-enzymatic oxidative decarboxylation of α-acetolactate and reduced to (3S)-AC by (S)-specific alcohol dehydrogenase. a parameter which is commonly used to express the enantiomeric composition of a sample. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other. Enantiomeric excess is defined as the absolute difference between the mole fraction of each enantiomer, namely ([R]−[S])/([R]+[S]) or ([S]−[R])/([R]+[S]), where [R] and [S] are the respective fractions of enantiomers in a mixture. an (S)-specific secondary alcohol dehydrogenase that catalyzes meso-2,3-BD production from (3R)-AC, (2S,3S)-2,3-BD production from (3S)-AC, and (3S)-AC production from diacetyl. It can be used to catalyze specific dehydrogenation of the (S)-hydroxyl group in meso-2,3-BD to produce (3R)-AC. an oxidoreductase that catalyzes the oxidation of NADH to NAD+ and reduces oxygen to H2O2 or H2O. NOX is an important tool for the regeneration of NAD+ in various biocatalytic system and recombinant microorganisms.