(161d) Design and Analysis of a Direct Pathway Process for the Enantioselective Production of Biomass-Derived (R)-?-Valerolactone

γ-valerolactone (GVL) is considered a key chemical in biorefineries. This is because GVL can be used for a variety of purposes, including fuel, solvent, and precursor to other products. However, the high cost of GVL has been a barrier to its commercialization. This high cost is due to the numerous reaction steps and complex separation processes required in conventional biorefinery processes. Therefore, we propose an improved approach that addresses the limitations inherent in conventional biorefineries to lower production costs.

Traditional biorefinery process typically involve the hydrolysis of biomass to sugars, followed by their fermentation or further processing into desired products. However, these multi-step paths suffer from inefficiencies due to significant product loss at multiple stages. To overcome these issues, we explored an improved method. These include one-step oxidation of biomass under harsh conditions, followed by an enzymatic reaction to produce GVL. Additionally, the enzymes used to produce GVL can produce GVL with high optical purity without the need for additional separation processes. Therefore, our strategy is to produce optically active GVL that has the potential to be utilized as pharmaceuticals (antileukemic steganacin or antihypertensive drugs) and sold at high prices.

The GVL produced from the proposed process can be utilized in various sectors of the chemical industry, contributing to the industry's progress toward the goal of carbon neutrality. Therefore, through this strategy, we aim to improve the economic and environmental viability of GVL to promote its widespread use.

Methods

In this study, we designed and evaluated a process to synthesize (R)-GVL from biomass composed of various components, following a pretreatment step and utilizing enzymatic reactions. Initially, lignocellulosic biomass underwent pretreatment using sulfuric acid under high temperature and pressure conditions (170°C, 7.8 atm), resulting in the production of levulinic acid (LA) and furfural (FF). At this stage, both cellulose and hemicellulose components were converted into LA in a one-step process and remained in the aqueous phase, leaving lignin as a solid residue.

Following this, lime was used to adjust the pH before separating the solid biomass residue from the liquid phase. The solid biomass residue was then separated into lignin and other components through a separation process. The lignin was utilized to make electrode materials for additional income. A portion of the liquid solvent was recycled back to the pretreatment reactor, with the remainder directed to the enzymatic reactor. Due to the enzymatic reactor's operation at a lower temperature (30°C) compared to the pretreatment reactor, significant energy was required to reduce the temperature of the stream. This necessitated the introduction of a separation process to decrease energy consumption and to efficiently utilize the thermal energy of the stream.

The stream entering the enzymatic reactor contained LA, which was converted into (R)-4-hydroxyvaleric acid ((R)-HA), and subsequently converted into (R)-GVL under acidic conditions. Following this, the components of the stream, including water, unreacted LA, FF, (R)-HA, and (R)-GVL, were efficiently separated. FF was converted into LA, and unreacted LA was recycled to produce more (R)-GVL. Unreacted HA was also separated to increase the efficiency of (R)-GVL production. The separated water was recycled back to the pretreatment reactor to fulfill the solvent requirements for the pretreatment reaction. Furthermore, to minimize energy consumption, heat integration was implemented within the process. A comparison was then made between our strategy and conventional (R)-GVL production strategies through a techno-economic analysis (TEA). Additionally, a cradle-to-gate life cycle assessment (LCA) was conducted to analyze the environmental impact factors from the raw material production stage to the (R)-GVL production process.

Results

The approach in this study efficiently utilized various components of the biomass with only a one-step pretreatment and simplified the reaction by converting the biomass to (R)-GVL via a highly optically selective enzymatic reaction. However, simplifying the reaction steps was not enough to reduce the cost of the process. Typically, integrating biological reactions operating at lower temperatures and pressures with chemical reactions operating at higher temperatures and pressures into a single integrated process required a significant amount of energy due to the large temperature difference. Therefore, we analyzed energy-intensive steps in the process and introduced appropriate separation processes to reduce energy consumption. Furthermore, by performing heat integration, we further reduced the amount of energy required, thus lowering the costs while simplifying reaction steps and optimizing the process.

To verify the economic feasibility of our process, we conducted a TEA. First, due to the small size and immaturity of the (R)-GVL market, we estimated the market price range of (R)-GVL using the market prices of products that can be made with (R)-GVL. As a result, we found that the market price range of (R)-GVL was higher than that of optically inactive GVL. The minimum selling price (MSP) of (R)-GVL produced in our process was 1517.3 $/ton and it was lower than the estimated market price range for (R)-GVL and within the market price range for optically inactive GVL, making it competitive even in the market for optically inactive GVL. Considering the current immaturity of the (R)-GVL market and the necessity for the produced (R)-GVL to be sold in the optically inactive GVL market, this process demonstrated economic feasibility not just for future scenarios but also at present. Moreover, compared to the MSP of the conventional process, (R)-GVL produced in our process showed a lower MSP, as the conventional process incurred high costs due to multiple reaction stages and purification steps, such as chiral chromatography, leading to a higher MSP.

Moreover, a cradle-to-gate life cycle analysis (LCA) was performed to assess the environmental impact of the proposed process. The results showed a global warming potential (GWP) of 2.33 kg CO₂ eq./kg GVL, which is lower than that of the conventional process. This is because the proposed process used less energy compared to the conventional process. It is especially notable that the factor with the most impact on GWP was lime (1.02 kg CO₂ eq./kg GVL), not heating requirement energy (0.65 kg CO₂ eq./kg GVL). This is due to the large pH difference between the pretreatment reactor and the enzyme reactor, which resulted in the use of a large amount of lime. The large pH difference is a limitation of this process and cannot be further improved in its current state. To improve the process from an environmental perspective, future efforts should focus on creating low-pH enzymes and researching high-pH pretreatment methods to reduce this difference.

Conclusion

In this study, we propose an innovative approach within the biorefinery sector, suggesting a method to enhance both economic viability and environmental sustainability. Unlike traditional approaches, this research develops a streamlined process for the production of optically active GVL, paving the way for a cost-effective alternative. As a result of the process design, we were able to reduce the MSP of (R)-GVL to 1517.3 $/ton, which is below the market price range of (R)-GVL and within the market price range of optically inactive GVL. Given the current state of the global GVL market, where the market size for optically active GVL is not large, a significant portion of the production must be sold in the market for optically inactive GVL. Therefore, this method, which reduces the MSP of (R)-GVL, presents commercial feasibility even at the current stage of the immature (R)-GVL market. Considering the potential market expansion for high-value products derived from (R)-GVL in the future, the commercialization prospects for (R)-GVL are expected to increase.

Furthermore, this approach allows for the reduction of the environmental impact. The findings suggest that the global warming potential of our process was 2.33 kg CO₂ eq./kg GVL, which is lower than the conventional process. Considering GVL's utility not only in its own right but also as an important platform chemical for producing other products, the given process signifies a substantial role in advancing toward carbon neutrality in the chemical industry. Through these analyses of economic and environmental benefits, this research underscores the necessity of an innovative approach that can improve both economic viability and environmental sustainability. Adopting various methodologies in biorefinery can contribute to a greener chemical industry.