1,3-Propanediol and 2,3-butanediol are two promising chemicals which have a wide range of applications and can be biologically produced. The separation of these diols from fermentation broth makes ...more than 50% of the total costs in their microbial production. This review summarizes the present state of methods studied for the recovery and purification of biologically produced diols, with particular emphasis on 1,3-propoanediol. Previous studies on the separation of 1,3-propanediol primarily include evaporation, distillation, membrane filtration, pervaporation, ion exchange chromatography, liquid-liquid extraction, and reactive extraction. Main methods for the recovery of 2,3-butanediol include steam stripping, pervaporation, and solvent extraction. No single method has proved to be simple and efficient, and improvements are especially needed with regard to yield, purity, and energy consumption. Perspectives for an improved downstream processing of biologically produced diols, especially 1,3-propanediol are discussed based on our own experience and recent work. It is argued that separation technologies such as aqueous two-phase extraction with short chain alcohols, pervaporation, reverse osmosis, and in situ extractive or pervaporative fermentations deserve more attention in the future.
•1,3-PD production was summarized in the view of bioprocess and bioengineering.•Microbial consortium has potential application for 1,3-PD production.•Salting-out and sugaring-out extraction have ...advantages for industrial production.•Microbial electrosynthesis is a novel technology for 1,3-PD production.•It represent challenges for efficient conversion of biomass hydrolysate to 1,3-PD.
1,3-Propanediol, a monomer for synthesis of polytrimethylene terephthalate, polyethers, polyurethanes, and heterocyclic compounds, has attracted worldwide attention. It can be produced from renewable resources using microorganisms, which focus mainly on the ecologically friendly process, industrial safety and sustainable development. This review summarized and commented in the view of bioprocess and bioengineering, especially on bioconversion of glycerol into 1,3-PD since 2010. Various strategies for microbial production of 1,3-PD from glycerol including strains screening and improvement, two-step and multi-stage fermentation, sole and co-substrate fermentation, co-culture, and microbial consortium were reviewed and compared. Besides experiments, theoretical analyses, such as fermentation kinetics, stability and robustness analysis, metabolic and system engineering analysis were also highlighted. The present strategies of the downstream processing of 1,3-PD were compared according to their advantages and drawbacks. Meanwhile, the novel technology of microbial electrosynthesis for biochemicals was well introduced and discussed. Finally, The future prospects and challenges of 1,3-propanediol from biotechnology were discussed for its industrial production.
To study the relationship between the yield of 1,3‐propanediol (1,3‐PDO) and the flux change of the Clostridium butyricum metabolic pathway, an optimized calculation method based on dynamic flux ...balance analysis was used by combining genome‐scale flux balance analysis with a kinetic model. A more comprehensive and extensive metabolic pathway was obtained by optimization calculations. The primary extended branches include: the dihydroxyacetone node, which enters the pentose phosphate pathway; the α‐oxoglutarate node, which has synthetic metabolic pathways for glutamic acid and amino acids; and the serine and homocysteine nodes, which produce cystathionine before homocysteine enters the methionine cycle pathway. According to the expanded metabolic network, the flux distribution of key nodes in the metabolic pathway and the relationship between the flux distribution ratio of nodes and the yield of 1,3‐PDO were analyzed. At the dihydroxyacetone node, the flux of dihydroxyacetone converted to dihydroxyacetone phosphate was positively correlated with the yield of 1,3‐PDO. As an important intermediate product, the flux change in the metabolic pathway of α‐oxoglutarate reacting with amino acids to produce glutamic acid is positively correlated with the yield. When pyruvate was used as the central node to convert into lactic acid and α‐oxoglutarate, the proportion of branch flux was negatively correlated with the yield of 1,3‐PDO. These studies provide a theoretical basis for the optimization and further study of the metabolic pathway of C. butyricum.
Traditional technology of cell disruption has become one of the bottlenecks restricting the industrialization of genetic engineering products due to its high cost and low efficiency. In this study, a ...novel bioprocess of phage lysis coupled with salting‐out extraction (SOE) was evaluated. The lysis effect of T7 phage on genetically engineered Escherichia coli expressing κ‐carrageenase was investigated at different multiplicity of infection (MOI), meanwhile the phage and enzyme released into the lysate were separated by SOE. It was found that T7 phage could lyse 99.9% of host cells at MOI = 1 and release more than 90.0% of enzyme within 90 min. After phage lysis, 87.1% of T7 phage and 71.2% of κ‐carrageenase could be distributed at the middle phase and the bottom phase, respectively, in the SOE system composed of 16% ammonium sulfate and 20% ethyl acetate (w/w). Furthermore, κ‐carrageenase in the bottom phase could be salted out by ammonium sulfate with a yield of 40.1%. Phage lysis exhibits some advantages, such as mild operation conditions and low cost. While SOE can efficiently separate phage and intracellular products. Therefore, phage lysis coupled with SOE is expected to become a viable alternative to the classical cell disruption and intracellular product recovery.
The inhibition of porcine pancreatic α-amylase and mammalian α-glucosidase by 16 individual flavonoids was determined. The IC50 values for baicalein, (+)-catechin, quercetin, and luteolin were 74.1 ± ...5.6, 175.1 ± 9.1, 281.2 ± 19.2, and 339.4 ± 16.3 μM, respectively, against α-glucosidase. The IC50 values for apigenin and baicalein were 146.8 ± 7.1 and 446.4 ± 23.9 μM, respectively, against α-amylase. The combination of baicalein, quercetin, or luteolin with acarbose showed synergistic inhibition, and the combination of (+)-catechin with acarbose showed antagonistic inhibition of α-glucosidase. The combination of baicalein or apigenin with acarbose showed additive inhibition of α-amylase at lower concentrations and antagonistic inhibition at a higher concentration. Kinetic studies of α-glucosidase activity revealed that baicalein alone, acarbose alone, and the combination showed noncompetitive, competitive, and mixed-type inhibition, respectively. Molecular modeling revealed that baicalein had higher affinity to the noncompetitive binding site of maltase, glucoamylase, and isomaltase subunits of α-glucosidase, with glide scores of −7.64, −6.98, and −6.88, respectively. (+)-Catechin had higher affinity to the active sites of maltase and glucoamylase and to the noncompetitive site of isomaltase. After sucrose loading, baicalein dose-dependently reduced the postprandial blood glucose (PBG) level in mice. The combination of 80 mg/kg baicalein and 1 mg/kg acarbose synergistically lowered the level of PBG, and the hypoglycemic effect was comparable to 8 mg/kg acarbose. The results indicated that baicalein could be used as a supplemental drug or dietary supplement in dietary therapy for diabetes mellitus.
Acetoin is one of the bio-based platform chemicals and its optically pure isomers are important potential intermediates and precursors in the synthesis of novel optically active materials. (
3R
...)-acetoin could be synthesized via enzymatic catalysis, whole-cell catalysis and fermentation. In this study a marine strain of
Bacillus subtilis
was isolated to produce optically pure (
3R
)-acetoin with glucose as carbon source. The effects of nutrients on the formation of (
3R
)-acetoin and conversion of glucose to (3
R
)-acetoin were evaluated by Plackett–Burman design, and the fermentation medium was optimized by central composite design. The impact of oxygen supply on the production of (3
R
)-acetoin was studied at different aeration rates. Under the optimal conditions, 83.7 g/L (
3R
)-acetoin with an optical purity of 99.4% was achieved by fed-batch fermentation, and the conversion of glucose to (3
R
)-acetoin was 91.5% of the theoretical value. The results indicate the industrial potential of this strain for (
3R
)-acetoin production via fermentation.
•A novel two-step salting-out extraction was used to separate 1,3-propanediol, butyric acid and acetic acid from fermentation broth.•Butyric acid could be separated from 1,3-propanediol and acetic ...acid by the salting-out extraction system comprised of acidic inorganic salt and hydrophobic solvent.•Effect of sodium carbonate concentration on the back-extraction of butyric acid was investigated.
The separation of 1,3-propanediol (1,3-PD), butyric acid (BA) and acetic acid (HAc) from the fermentation broth was studied by two-step salting-out extraction. In the first salting-out extraction, the partition coefficient and recovery of BA reached 42.21 and 96.42%, respectively, under the optimal condition of 25 wt% NaH2PO4/30 wt% n-butyl acetate. Subsequently, 91.28% of BA in the organic phase could be recovered through back-extraction when sodium carbonate solution was mixed with organic phase with initial phase ratio of n-butyl acetate solution to alkaline solution being 2:1, in which the molar ratio of sodium carbonate to organic acids was 3:5. Finally, 50% (v/v) ethanol (95%) was added to the bottom phase for the second step salting-out extraction. And the partition coefficient and recovery of 1,3-PD were 9.40 and 95.50%, and those of HAc were 7.46 and 94.40%, respectively. All the cells and most of the proteins (97.16%) could be removed. Effective separation of 1,3-PD from BA was realized by two-step salting-out extraction, which provides a potential method for separation of 1,3-PD, BA and HAc on an industrial scale.
•Phase forming abilities of hydroxylammonium ionic liquids with K3PO4 were studied.•Acetoin partition behavior in ionic liquid-K3PO4 system was studied.•93% acetoin and 76% ethanolammonium butyrate ...were distributed into the top phase.•The selectivity of acetoin over lactic acid and acetic acid was 16.46 and 3.85.•IR spectra showed the intermolecular hydrogen bonds between acetoin and ILs.
The salting-out extraction (SOE) systems based on ionic liquids (ILs) have attracted extensive attention in the separation of bio-based products, in which imidazolium ILs were widely studied. However, the high cost and toxicity have hindered their further industrial application. Hydroxylammonium ILs have the characteristics of cheap raw material, simple synthesis process and low toxicity, but are rarely used in the SOE systems. In this work, five hydroxylammonium ILs (2 cations and 4 carboxylate anions) were synthesized and used in SOE of bio-chemicals. The phase forming abilities of ILs with K3PO4 and H2O were affected by the hydrophilicity of anions and cations. With the increase of carbon chain length, phase forming abilities of ILs increased, while the temperature had little influence. The partition behaviors of acetoin, ILs and 2,3-butandiol, and the selectivity of acetoin to organic acids were investigated and compared at different concentrations of ethanolammonium butyrate (EOAB) and K3PO4. In a SOE system consisted of 6% EOAB-38% K3PO4 (w/w), the recovery of acetoin, IL and 2,3-butandiol was 92.7%, 76.0% and 86.0%, respectively, and the selectivity of acetoin to lactic acid and acetic acid was 16.46 and 3.85, respectively. The ATR-IR spectra showed the hydrogen bonds formed between acetoin and O-H, N-H, –COO– of hydroxylammonium IL played an important role in the efficient extraction of acetoin from fermentation broths.
