Prof. Ning Yan obtained his BS and PhD degrees from Peking University in 2004 and 2009, respectively. Thereafter, he worked as a Marie-Curie research fellow at École Polytechnique Fédérale de Lausanne, Switzerland. He joined the National University of Singapore (NUS) as an assistant professor, established the Lab of Green Catalysis in 2012, and was promoted to the position of associate professor in 2018.Yunzhu Wang received her BE degree from NUS in 2014. She joined Prof. Yan’s group in the same year and is currently pursuing her PhD. Her research interests include nanoscale metal catalysts and their applications in producing renewable nitrogen-containing chemicals. Prof. Ning Yan obtained his BS and PhD degrees from Peking University in 2004 and 2009, respectively. Thereafter, he worked as a Marie-Curie research fellow at École Polytechnique Fédérale de Lausanne, Switzerland. He joined the National University of Singapore (NUS) as an assistant professor, established the Lab of Green Catalysis in 2012, and was promoted to the position of associate professor in 2018. Yunzhu Wang received her BE degree from NUS in 2014. She joined Prof. Yan’s group in the same year and is currently pursuing her PhD. Her research interests include nanoscale metal catalysts and their applications in producing renewable nitrogen-containing chemicals. Amino acids are central to life on earth. They are also essential chemicals used in myriad applications, including food, feed, and pharmaceuticals, as well as building blocks in the industrial synthesis of bio-based plastics and other compounds of value to humanity. The past 10 years have witnessed an expeditious growth of amino acid manufacturing, whose global sales reached $20 billion in 2014 and are expected to exceed $35 billion by 2022.1Radiant InsightsAmino acids market size & research report, 2022.https://www.radiantinsights.com/research/amino-acids-marketDate: 2015Google Scholar However, not many tools in chemists’ toolbox can produce amino acids. One of the earliest methods, the Strecker synthesis, was reported in 1850.2Strecker A. Ueber die künstliche Bildung der Milchsäure und einen neuen, dem Glycocoll homologen Körper.Ann. Chem. Pharm. 1850; 75: 27-45Crossref Scopus (945) Google Scholar In this method, an imine derived from the condensation of an aldehyde with NH4Cl is treated with aqueous HCN, forming an intermediate in which an amine and nitrile group are both attached to the desired α-position. The nitrile group is then hydrolyzed into a carboxyl group to form an amino acid. A distinct disadvantage of this route is the use of highly toxic HCN as feedstock. Another chemical approach to amino acids is the Gabriel malonic ester synthesis, where an N-phthalimidomalonic ester is alkylated at the α-position with an alkyl halide. Acid hydrolysis and thermal decarboxylation then reveal the primary amine and carboxylic acid. A final example is Miller’s famous experiment, which transformed methane, ammonia, water vapor, and hydrogen into amino acids by subjecting the mixture to continuous electrical sparks, mimicking the primeval atmosphere. Four α-amino acids were identified in Miller’s original report, and over a dozen more have been added to the list by re-examination of the sealed vials preserved from the original experiments via advanced electrospray mass spectrometry techniques.3Parker E.T. Cleaves H.J. Dworkin J.P. Glavin D.P. Callahan M. Aubrey A. Lazcano A. Bada J.L. Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment.Proc. Natl. Acad. Sci. USA. 2011; 108: 5526-5531Crossref PubMed Scopus (177) Google Scholar Nature does not use these methods to make amino acids; instead, it uses biomass—carbohydrates in particular—to make amino acids, from which proteins are assembled. Indeed, chemists’ success in amino acid manufacturing remains limited. Only methionine is chemically produced by Strecker synthesis, which uses methyl mercaptan, acrolein, HCN (or other sources of cyanide), ammonium ions, and a strong mineral acid as feedstock. Even though this process has been commercialized for over half a century and has an annual global capacity of one million tons, alternative sustainable processes based on natural resources have emerged as the subject of increasing interest.4Willke T. Methionine production--a critical review.Appl. Microbiol. Biotechnol. 2014; 98: 9893-9914Crossref PubMed Scopus (99) Google Scholar This is unsurprising given the prospect of dwindling fossil resource reserves and increasingly stringent environmental regulations. Current amino acid production is largely based on microbial conversion processes. l-Glutamate, l-lysine, l-threonine, and l-isoleucine production using Corynebacterium glutamicum is well established in industry, but these bio-based processes are not without problems. Biological conversion processes are typically slow, requiring days for efficient production of target products. Furthermore, C. glutamicum cultivation processes are aerobic. This necessitates large, energy-intensive compressors to pump air through bioreactors, which significantly increases energy usage and costs and inherently limits the scale of amino acid production. Additionally, the separation of amino acids from bio-based intermediates, especially acids, drives up the cost of the process and generates a significant amount of waste salt. Given the challenges encountered in bio-based amino acid production, there are substantial opportunities for chemists to develop robust chemo-catalytic processes from renewable sources, such as biomass. Under the concept of biorefineries, a number of catalytic processes to transform various types of biomass or biomass components—such as cellulose, hemicellulose, lignin, lipids, and chitin—into value-added chemicals have been developed in the last two decades, which has been a testament to the power of chemical catalysis in biomass valorization. Unfortunately, a sustainable and generalizable approach to using NH3 for the direct synthesis of amino acids from abundant and renewable feedstocks remains a rarity. This is partly due to the “functional-group gap” that exists between amino acids and biomass components. The former group contains amine groups and carboxyl groups, which are absent in the latter. Considering that biomass components are rich in oxygen but lack nitrogen (with the exception of chitin), a rational approach to making amino acids would be to transform oxygen-containing groups into carboxyl groups while introducing amine groups at the desired α-position. With this in mind, we recently developed a two-step protocol to make several amino acids from sugars.5Deng W. Wang Y. Zhang S. Gupta K.M. Hülsey M.J. Asakura H. Liu L. Han Y. Karp E.M. Beckham G.T. et al.Catalytic amino acid production from biomass-derived intermediates.Proc. Natl. Acad. Sci. USA. 2018; 115: 5093-5098Crossref PubMed Scopus (128) Google Scholar The first step prepares α-hydroxy acids by catalytic transformations of polysaccharides, lignin, and their derivatives according to procedures reported in the literature. After that, the hydroxyl groups are replaced by amine groups to access a series of α-amino acids. To this end, a supported Ru catalyst with high efficiency and recyclability was developed for the desired conversion, allowing six amino acids to be generated from their corresponding α-hydroxy acids. Based on the catalytic system developed in the study, a new two-step chemical process to convert glucose into alanine in 43% yield was demonstrated. This yield is comparable to some of the best values obtained in microbial cultivation processes and leaves considerable room for further improvement. Moreover, a conceptual process design employing membranes to facilitate product purification was proposed and validated by membrane distillation. Altogether, this improved chemical process could conceivably compete with the microbial conversion processes in current use given that it provides higher space-time productivity and cost-effective, facile separations. The amination reaction developed in this work is reminiscent of Miller’s classical experiment. Apart from methane and electrical sparks, which are replaced by biomass-derived α-hydroxy acids and a heterogeneous Ru catalyst, respectively, all the other reagents are surprisingly identical. Instead of obtaining a mixture of amino acids, the reaction obtains a single specific amino acid each time. Related work is also emerging from other groups. N-acetylglucosamine, the monomer of chitin, has been converted into a glycine derivative with the use of a Ru/C catalyst.6Techikawara K. Kobayashi H. Fukuoka A. Conversion of N-acetylglucosamine to protected amino acid over Ru/C catalyst.ACS Sustain. Chem. Eng. 2018; 6: 12411-12418Crossref Scopus (32) Google Scholar In another published work, glutamic acid isolated from waste gluten via microwave-assisted hydrolysis was subsequently transformed into γ-aminobutyric acid via a decarboxylation reaction.7Lie Y. Farmer T.J. Macquarrie D.J. Facile and rapid decarboxylation of glutamic acid to γ-aminobutyric acid via microwave-assisted reaction: towards valorisation of waste gluten.J. Clean. Prod. 2018; 205: 1102-1113Crossref Scopus (17) Google Scholar Despite these advances, the chemical production of amino acids from renewable resources remains in its infancy. By harnessing the structural features of bio-based waste materials, we envisage a number of interesting routes toward various amino acids (Figure 1). Every year, 3.5 million tons of raw glycerol are produced as a major side product of biodiesel manufacturing.8Lari G.M. Pastore G. Haus M. Ding Y. Papadokonstantakis S. Mondelli C. Pérez-Ramírez J. Environmental and economical perspectives of a glycerol biorefinery.Energy Environ. Sci. 2018; 11: 1012-1029Crossref Google Scholar Previous studies have demonstrated that glycerol can be transformed into several oxygen-containing chemicals, including lactic acid. Combining this known transformation with the newly developed amination chemistry would enable alanine formation from glycerol in two steps. A more ambitious approach is the direct, one-pot production of alanine from glycerol via sequential dehydrogenation, dehydration, rearrangement, and amination steps. Hemicellulose, enriched with 5-carbon sugars, is a suitable starting material for 5-carbon amino acids, such as glutamic acid and proline. A plausible route for glutamic acid synthesis starts with xylose amination, followed by terminal alcohol oxidation and hydroxyl group deoxygenation. Hemicellulose-derived furfural is an ideal starting material for proline via oxidation, amination, and hydrogenation. Although these two reaction sequences have not been reported, the chemistry of each step is well known. Cellulose is a suitable feedstock for several amino acids, such as glycine. Glycine is the simplest amino acid containing two carbons and could be obtained by the oxidation of ethanolamine, which is available from cellulose.9Liang G. Wang A. Li L. Xu G. Yan N. Zhang T. Production of primary amines by reductive amination of biomass-derived aldehydes/ketones.Angew. Chem. Int. Ed. 2017; 56: 3050-3054Crossref PubMed Scopus (199) Google Scholar Lignin, on the other hand, is an ideal source for aromatic amino acids. We envisage tyrosine synthesis from lignin via p-coumaric acid as a key intermediate. Finally, chitin, the most abundant nitrogen-containing biopolymer on earth, holds a unique position for accessing amino acids. The most direct transformation is to produce glucosaminic acid via consecutive hydrolysis, deacetylation, and oxidation reactions. Considering the high market value and demand for amino acids, these routes will enhance the economic viability of the biorefinery once they have been established. There are broader implications when it comes to the chemical synthesis of amino acids from biomass. In the ecosystems on earth, solar energy is fixed by primary producers, such as green plants, into chemical energy. From there, the energy flows into primary consumers, such as herbivores. Photosynthesis is the key chemical step in the first level of the ecosystem by converting carbon from inorganic forms to organic forms. At the second level of the ecosystem, amino acid synthesis is key for transforming lignocellulosic-enriched species into protein-enriched species. In contrast to the tremendous progress in the field of artificial photosynthesis, we have done little by way of developing amino acid synthesis from biomass. This transformation is more important than many would think. From a chemist’s or chemical engineer’s point of view, cattle breeding is a highly inefficient process: 95% of the carbon that goes into a cow ends up as solid excrement or gaseous waste, such as methane and CO2. Indeed, agriculture is responsible for 24% of greenhouse gas emissions, which is more than the entire transportation sector’s contribution.10Food and Agriculture Organization of the United NationsGreenhouse gas emissions from agriculture, forestry and other land use (United Nations).http://www.fao.org/3/a-i6340e.pdfDate: 2016Google Scholar When one considers that only 10% of the chemical energy stored in primary producers is transferred to primary consumers, there is ample room for chemists and chemical engineers to bring about improvement by practicing their craft. To this end, a number of challenges and opportunities remain. Because most amino acids are more useful in their chiral form, developing a chiral synthesis of amino acids from biomass stands as a grand challenge. Alternatively, can we separate the enantiomers of a racemic mixture of amino acids in a simpler and more cost-effective manner? Although there has been significant progress in enantioselective crystallization processes, extending these protocols to the manufacture of amino acids on an industrial scale remains underdeveloped. Meanwhile, current amino acid purification relies on energy-intensive distillation-recrystallization processes. Can we develop and commercialize more advanced techniques, such as membrane technology, to purify the products? In the longer term, can we assemble amino acids into oligomers and proteins in a rapid, affordable, and predictable manner so that upgraded nutrition from biomass waste becomes viable? Addressing these issues is not simply a matter of academic curiosity but would also help to place the world on a more sustainable trajectory. Reaction: A New Option for Producing Amino Acids from Renewable Biomass?Ge et al.ChemApril 11, 2019In BriefJunwei Ge received his PhD degree in chemistry from Wuhan University in 2013 and now is a senior engineer at the SINOPEC Shanghai Research Institute of Petrochemical Technology (SRIPT).Yuqing Jia received her PhD degree in chemistry from Peking University in 2015 and now is a senior engineer at SRIPT.Qi Song received his PhD degree in chemistry from the Dalian Institute of Chemical and Physics of the Chinese Academy of Sciences in 2013 and now is a senior engineer at SRIPT.Prof. Weimin Yang received his PhD degree in physical chemistry from Nanjing University in 1994 and now is the president of SRIPT and director of the State Key Laboratory of Green Chemical Engineering and Industrial Catalysis. His research interests mainly focus on the study and development of novel technologies in energy-saving and pollution-reducing chemical engineering for petrochemicals. Full-Text PDF Open ArchiveReaction: Proteins from Chemocatalysis; It’s What’s for DinnerEllis et al.ChemMay 20, 2019In BriefLucas D. Ellis received his BS from California Polytechnic State University, MS from Dartmouth College, and PhD focusing on heterogeneous catalysis from the University of Colorado. He is currently a Director’s Postdoctoral Fellow at the National Renewable Energy Laboratory (NREL). His research focuses on developing heterogeneous catalysts and chemical processes capable of reducing the impact of climate change. Gregg T. Beckham is a senior research fellow at NREL. He received a PhD and MSCEP from the Massachusetts Institute of Technology and a BS from Oklahoma State University. He currently leads an interdisciplinary team on the conversion of biomass to chemicals and materials and in the area of plastics upcycling. Full-Text PDF Open Archive