The potential of converting carbon dioxide to food compounds via asymmetric catalysis

The food crisis caused by diminished arable land, extreme weather and climate change linked to increased carbon dioxide (CO2) emission, is threatening global population growth. Interestingly, CO2, the most widespread carbon source, can be converted into food ingredients. Here, we briefly discuss the progress and challenges in catalytic conversion of CO2 to food ingredients via chiral catalysis.

developed in order to obtain high-purity acetic acid and avoid complex isolation and purication steps. Finally, high-purity acetic acid was utilized as the feedstock for genetically engineered Saccharomyces cerevisiae fermentation, which delivers an average D-glucose yield of 8.90 mmol per gram of yeast per hour. In addition to D-glucose, the production of other valuable products was also showcased by taking advantage of this platform. For example, using a similar design, the researchers engineered strain LXJ015 to electrically produce free fatty acids in vitro from pure acetic acid (Fig. 1). 2 Earlier, Cai et al. reported a chemical-biochemical hybrid pathway for the synthesis of starch from CO 2 and hydrogen in a cell-free system through 11 core enzyme-catalyzed reactions. 3 Starch is the most important carbohydrate utilized by people. In this research, CO 2 was rst reduced to a C1 compound (formic acid or methanol) using a chemical catalyst. The C1 compound was then utilized as a substrate for the articial starch anabolic pathway (ASAP) system developed by the same researchers. In the ASAP system, they divided the starch synthesis into a C1 module (for formaldehyde production), C3 module (for Dglyceraldehyde-3-phosphate production), C6 module (for Dglucose-6-phospate production), and Cn module (for starch synthesis). The enzymatic processes were delicately combined with the chemical catalysis processes, and each module of the enzymatic processes was optimized by mutating the core enzymes of catalytic pathways, namely, formolase, fructosebisphosphatase, and ADP-glucose pyrophosphorylase. Finally, an ASAP 3.0 system, composed of C1e, C3a, C6b*, and Cnb modules, was determined with 10 enzyme-catalyzed reactions using methanol as the substrate. This system delivered a remarkably high starch productivity of ∼410 mg L −1 h −1 from CO 2 . This landmark work provides for the rst time a way to convert waste CO 2 into an economically valuable food ingredient via a combination of chemical catalysis, biosynthesis, and protein engineering (Fig. 2). 3 As an emerging area in CO 2 utilization, the two studies mentioned above not only open new strategies for preparing food products by combining electrochemistry with biocatalysis, but also provide potential solutions to alleviate the food crisis. Nonetheless, both studies synthesize chiral food ingredients from CO 2 by taking advantage of chiral biological systems. Strictly speaking, it is not a direct route to transform CO 2 to chiral food ingredients, since two separate processes, chemical transformation and biological transformation, were integrated in both studies. The former harvests achiral C1 compounds or C2 compounds, while the latter delivers chiral compounds by utilizing the asymmetric catalytic transformation function of biological systems.
So far, the chemo-catalytic conversion of CO 2 into chiral compounds with specic congurations, especially chiral food components (amino acids, monosaccharides, and fatty acids), has been slow to develop. This could be attributed to the following challenges that hinder the development of an operable technology for the direct asymmetric conversion of CO 2 . First, CO 2 is a very stable and inert molecule since it is in the lowest energy state, and the carbon in CO 2 is in its most stable valence (IV). Second, it is rather difficult for CO 2 to approach metal catalysts because of its weak coordination ability with metal catalysts and low solubility in non-alkaline solvents. Third, direct asymmetric conversion of achiral CO 2 into chiral food ingredients requires a complex and tedious organic chemical synthesis process, and the derived products from the catalytic processes are oen mixed enantiomers, which require an expensive enantiomeric sieving process. Furthermore, because of the inert nature of CO 2 , its catalytic conversion usually requires high temperature and high pressure, which are not conducive to the preparation of chiral compounds with specic congurations. 4 In conclusion, chemical methods for the catalytic conversion of CO 2 into valuable chiral chemicals are feasible, but the synthesis of chiral food components still requires process optimization and cost reduction, which inspire us to search for efficient catalytic pathways and chiral catalysts for this challenging chemical transformation.

Asymmetric catalysis
Asymmetric catalysis, also known as chiral catalysis, renders catalytic reactions to proceed in the direction of the mirror isomers that match chiral catalysts, thereby enabling the controlled synthesis of chiral compounds with various specic congurations. Because of the chiral amplication effect, it is one of the most effective methods for synthesizing chiral products. 5 The key to chiral catalytic reactions is the development of efficient chiral catalysts. In recent years, due to the combined amplication effect 6 of chirality in asymmetric catalysis with the excellent opto-electromagnetic properties of nanomaterials, 7 chiral nanomaterials have received increasing attention, 8 and great progress has been made in the eld of asymmetric catalysis. 9 For example, Zhang et al. reported versatile and efficient asymmetric cross-coupling between carbonyl radicals (from aldehydes) and aryl radicals (from aryl halides) by utilizing porous chiral metal-organic frameworks as catalysts under light illumination. 10 Wei et al. accomplished the dimerization of a specic conguration of the prochiral molecule 2-anthracenecarboxylic acid under light by controlling the chirality of metal nanohelices which were produced by glancing-angle deposition on the substrates rotated in the clockwise or counterclockwise direction. 11 Chiral nanomaterials also exhibit fascinating asymmetric catalytic functions relevant to biocatalysis. 12 In addition, compared with enzymes, nanomaterials cost less and have good environmental stability. Importantly, nanomaterial catalytic products oen require only simple centrifugal separation to obtain high purity of the targets. Our group has demonstrated that chiral CdTe quantum dots with the function of restriction endonuclease can specically cut DNA, and the cleavage efficiency is dependent on the conguration of the chiral CdTe quantum dots. 13 Chiral Cu 1.96 S nanoparticles (NPs) and Cu 2 S NPs have been reported to display chiral-conguration-dependent cleavage capability for the tobacco mosaic virus capsid protein 9 and hepatitis B core antigen, 14 respectively. Chiral nanoparticles can also catalyze the polymerization of some biomolecules. Li et al. reported that chiral nanoscale inorganic superparticles can serve as photocatalysts that enantioselectively catalyze L-tyrosine and D-tyrosine into L-dityrosine and D-dityrosine, respectively. 12 Therefore, asymmetric catalysis based on chiral nanomaterials is thriving and could become an important direction for the direct asymmetric catalytic conversion of CO 2 to chiral food ingredients. Nonetheless, catalytic conversion of CO 2 into chiral food components inevitably involves complex processes including carbon chain elongation, polymerization, amination, sulfurization, etc. Access to readily available and easily convertible chiral intermediates is the key to the direct synthesis of food ingredients from CO 2 . Next, we briey describe how to obtain potential chiral intermediates from CO 2 since they are indispensable for the preparation of more complex chiral food components.

Progress in direct catalytic conversion of CO 2 into chiral intermediates
To date, asymmetric catalytic conversion of CO 2 into chiral intermediates can be mainly divided into the categories of asymmetric C-O bonds, asymmetric C-N bonds, asymmetric C-C bonds, and asymmetric C-H bonds on the basis of the products formed.
The formation of asymmetric C-O bonds refers to the bonding method where the carbon atoms of CO 2 become chiral carbon atoms aer the addition of oxygen from reactants. The Fig. 2 Design of an artificial starch anabolic pathway (ASAP) system that converts CO 2 to starch. CO 2 is first reduced to one-carbon units (C1), such as methanol. Then, methanol is oxidized to formaldehyde (FADH). FADH is treated with formolase (FLS) to produce dihydroxyacetone (DHA). Then, DHA is phosphorylated to form dihydroxyacetone phosphate (DHAP). DHAP is treated with triose phosphate isomerase (TPI) to from D-glyceraldehyde 3-phosphate (GAP). So far, the synthesis of three-carbon units (C3) has been completed. Next, GAP is treated with (FBA) to form D-fructose-1,6-bisphosphate (F-1,6-BP). Then, F-1,6-BP is treated with fructose-bisphosphatase (FBP) to form D-fructose-6-phosphate (F-6-P). F-6-P is then treated with phosphoglucose isomerase (PGI) to form D-glucose-6-phosphate (G-6-P). The presence of G-6-P implies the successful preparation of six-carbon units (C6). After that, G-6-P is treated with phosphoglucomutase (PGM) to form D-glucose-1-phosphate (G-1-P). Then, G-1-P is treated with ADP-glucose pyrophosphorylase to form ADP glucose (ADPG). ADPG then is treated with starch synthase (SS) to form starch. This is the final composite module (Cn) of the ASAP system (ref. 3).
formation of asymmetric C-O bonds can be achieved by either asymmetric nucleophilic attack on CO 2 by O-nucleophiles 15 or kinetic resolution of epoxides with CO 2 . 16 Strategies for constructing chiral C-O bonds directly on carbon radical centers are attractive, but the control over stereoselectivity remains a formidable challenge. Zhu et al. reported a copper-catalyzed regioselective and enantioselective carboesterication of substituted dienes using alkyl diacyl peroxides as the source of both carbon and oxygen substituents. This work represents a striking advance in the development of asymmetric radical C-O bonds and may lead to the discovery of other asymmetric radical reactions. 15 Lu et al. found that chiral cyclic carbonates can be synthesized by employing cobalt(III)-based complexes as chiral catalysts and the nucleophiles as cocatalysts during the kinetic resolution of racemic propylene oxide and CO 2 . 17 Jing et al. realized the kinetic resolution of epoxides and CO 2 with an ee value of 52% by loading Ni-based chiral catalyst into a threedimensional porous metal-organic framework and using n-Bu 4 NBr as a cocatalyst. 18 North et al. declared that cyclic carbonates can be synthesized over a dinuclear chiral catalyst consisting of a chiral Al(III)-based catalyst and a Cr(III)-based catalyst in the presence of n-Bu 4 NBr as a cocatalyst. 19 Johnston and coworkers developed an elegant strategy to produce chiral cyclic carbonates via the carboxylation/alkene functionalization reaction of homoallylic alcohols. They also conrmed that a properly balanced Brønsted acid/base bifunctional catalyst lowers the barrier of CO 2 incorporation and facilitates the stabilization of the resulting adduct, which are essential for the nucleophilic addition of a nucleophile to CO 2 (Fig. 3). 20 The formation of asymmetric C-N bonds implies that the carbon atoms of CO 2 become chiral following the nitrogen addition reaction. The asymmetric C-N bond formation can be realized by either asymmetric nucleophilic attack on CO 2 by Nnucleophiles 21 or asymmetric carboxylation of amines and their derivatives with CO 2 using chiral catalysts. 22 In the former case, Zhang et al. synthesized chiral allyl carbamate from CO 2 by the catalytic domino reaction for the rst time with a high ee value of 94%. 23 In the latter case, Zheng et al. found that the nucleophilic addition of CO 2 using amine nucleophiles can enantioselectively convert allyl carbonate to branched-chain carbamate with an ee value up to 93% (Fig. 4). 24 In a similar way, the formation of asymmetric C-C bonds and asymmetric C-H bonds signies that the carbon atoms of CO 2 become chiral aer reaction products are formed. Asymmetric C-C and C-H bonds 25 can be formed directly via an enantioselective nucleophilic attack on CO 2 by organometallic reagents. For example, directly catalyzed asymmetric binding of CO 2 to unsaturated hydrocarbons is considered as an attractive CO 2 chemical xation scheme. Studies have shown that copperbased catalysts can catalyze both the reduction of two prochiral conjugated olens and the restoration of the product. This allows for enantioselective synthesis of organoboron derivatives with multiple adjacent stereocenters in the presence of diboron compounds. 26 Another study demonstrated that palladium- based catalysts can catalyze the enantioselective C-H alkylation of allyl groups to yield chiral g,d-unsaturated amides. 27 While progress has been made in the formation of asymmetric C-C and asymmetric C-H bonds, a general method has not been fully developed. It is also worth noting that some nucleophiles possess both N-nucleophilic and O-nucleophilic addition functions. In this case, the formation of asymmetric C-O bonds, asymmetric C-N bonds, and asymmetric C-H bonds may be accompanied by the formation of asymmetric C-C bonds due to the presence of different nucleophilic adducts. The generation of these chiral compounds makes it possible to directly catalyze CO 2 into chiral food components (Fig. 5).
The potential of directly converting CO 2 to chiral food compounds Excitingly, some reports on the synthesis of chiral amino acids from CO 2 are already available. 21,28 These pioneering studies conrm that the formation of asymmetric C-N bonds can facilitate the synthesis of a-amino acids with specic congurations. Signicant progress has also been made in the asymmetric carboxylation of amines and their derivatives with CO 2 by using chiral catalysts to synthesize a-amino acids with high ee values. On the basis of the asymmetric catalytic function of vitamin B6, Cai et al. developed a variety of chiral biomimetic catalytic systems, leading to various chiral amine compounds such as a-amino acids and peptides via biomimetic asymmetric transamination and carbonyl-catalyzed a-C-H asymmetric functionalization of primary amines. 21 Moreover, the obtained a-amino acids can be further polymerized to form high-order chiral poly-amino acids by meticulously selecting specic chiral catalysts (Fig. 6). 28 Although asymmetric catalytic conversion of CO 2 has made tremendous progress in the past few decades, direct catalytic conversion of CO 2 into chiral food components is still challenging. Currently, only a limited number of studies on the synthesis of amino acids and short peptides using CO 2 exist. The scientic progress in this eld is far behind to meet the needs for sufficient food, especially carbohydrates, for the world's growing population. Direct catalytic conversion of CO 2 to synthesize carbohydrates, functional peptides, and proteins will help relieve the food crisis, but still faces huge obstacles. For example, D-glucose and its aggregates (starch) are the most important carbohydrates utilized by human beings; however, articial synthesis of D-glucose suffers from complex and tedious separation and purication of chiral congurations. In addition, compared to biocatalysis, the chiral catalysis of carbon dioxide conversion can effectively separate the two enantiomer products by designing the chiral conguration of the catalyst. Thus, the rapid development of asymmetric catalysis based on chiral nanomaterials provides enormous opportunities for the direct conversion of CO 2 into chiral food components.

Conflicts of interest
The authors declare no competing interests.