Wohlgemuth, Roland

Wohlgemuth R.

Sustainable processes by completing biocatalytic conversions and recovering products completely.

Malzacher S., Meißner D., Range J., Findrik Blažević Z., Rosenthal K., Woodley J.M., Wohlgemuth R., Wied P., Nidetzky B., Giessmann R.T., Prakinee K., Chaiyen P., Bommarius A.S., Rohwer J.M., de Souza R.O., et. al.

Biocatalysis needs improved reproducibility and quality of research reporting. Our interdisciplinary team has developed a flexible and extensible metadata catalogue based on STRENDA guidelines, essential for describing complex experimental setups in biocatalysis. The catalogue is available online via GitHub for community use.

Wohlgemuth R.

Enzyme catalysis was traditionally used by various human cultures to create value long before its basic concepts were uncovered. This was achieved by transforming the raw materials available from natural resources into useful products. Tremendous scientific and technological progress has been made globally in understanding what constitutes an enzyme; what reactions enzymes can catalyze; and how to search, develop, apply, and improve enzymes to make desired products. The useful properties of enzymes as nature’s preferred catalysts, such as their high selectivity, diversity, and adaptability, enable their optimal function, whether in single or multiple reactions. Excellent opportunities for the resource-efficient manufacturing of compounds are provided by the actions of enzymes working in reaction cascades and pathways within the same reaction space, like molecular robots along a production line. Enzyme catalysis plays an increasingly prominent role in industrial innovation and responsible production in various areas, such as green and sustainable chemistry and industrial or white biotechnology. Sources of inspiration include current manufacturing or supply chain challenges, the treasure of natural enzymes, and opportunities to engineer tailor-made enzymes. Making the best use of the power of enzyme catalysis is essential for changing how current products are manufactured; how renewable biobased resources can replace fossil-based resources; and improving the safety, health, and environmental aspects of manufacturing processes to support cleaner and more sustainable production.

Wohlgemuth R.

Enzyme catalysis has traditionally been used by various human cultures for creating value, long before its basic concepts have been uncovered, by preparing useful products through the trans-formation of raw materials available from natural resources. Tremendous scientific and techno-logical progress has been accumulated globally in understanding what constitutes an enzyme, what reactions enzymes can catalyze, and how to search, develop, apply and improve enzymes to make desired products. The exquisite properties of enzymes as nature's preferred catalysts, such as high selectivity, diversity and adaptability, enable their optimal work, whether in single reactions or in multiple reactions. Excellent opportunities for resource efficient manufacturing of compounds needed are provided by the actions of enzymes working in reaction cascades and pathways within the same reaction space, like molecular robots along a production line. Enzyme catalysis plays an increasing role for industrial innovation and responsible production in various areas, such as green and sustainable chemistry, industrial or white biotechnology. Sources of inspiration can be current manufacturing or supply chain challenges, the treasure of natural enzymes or the opportunities of engineering tailor-made enzymes. Making best use of the power of enzyme catalysis is essential for changing the way how current products are manufactured, how renewable biobased resources can replace fossil-based resources, and how the safety, health environment aspects of manufacturing processes can be improved towards cleaner and more sustainable production.

Hardt N., Kind S., Meier R., Schoenenberger B., Eggert T., Obkircher M., Wohlgemuth R.

Wohlgemuth R.

Alcántara A.R., Alghiffary F.I., Claassen C., de Gonzalo G., de Melo E.M., de Souza R.O., Domínguez de María P., Finnigan W., Franconetti A., Gamenara D., Guajardo N., Kara S., Lončar N., Mangas-Sánchez J., Marić I., et. al.

Wohlgemuth R.

The architecture, organization, and functioning of biocatalytic reaction networks, which are coded in the cell-specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. Knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary that is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions, or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims to outline advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

Wohlgemuth R.

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

Wohlgemuth R.

Methodologies for the synthesis and purification of metabolites, which have been developed following their discovery, analysis, and structural identification, have been involved in numerous life science milestones. The renewed focus on the small molecule domain of biological cells has also created an increasing awareness of the rising gap between the metabolites identified and the metabolites which have been prepared as pure compounds. The design and engineering of resource-efficient and straightforward synthetic methodologies for the production of the diverse and numerous metabolites and metabolite-like compounds have attracted much interest. The variety of metabolic pathways in biological cells provides a wonderful blueprint for designing simplified and resource-efficient synthetic routes to desired metabolites. Therefore, biocatalytic systems have become key enabling tools for the synthesis of an increasing number of metabolites, which can then be utilized as standards, enzyme substrates, inhibitors, or other products, or for the discovery of novel biological functions.

Wohlgemuth R.

Methodologies for the synthesis and purification of metabolites, which have been developed following their discovery, analysis and structural identification, have been involved in numerous life science milestones. The renewed focus on the small molecule domain of biological cells has also created an increasing awareness of the rising gap between the metabolites identified and the metabolites which have been prepared as pure compounds. Due to the large number and molecular diversity of metabolites the design and engineering of resource-efficient and straightforward synthetic methodologies for their production have attracted much interest. The variety of metabolic pathways in biological cells provide a wonderful blueprint for designing simplified and resource-efficient synthetic routes to desired metabolites. Therefore, biocatalytic systems have become key enabling tools for the synthesis of an increasing number of metabolites, which can then be utilized as standards, enzyme substrates, inhibitors or products, or for the discovery of novel biological functions.

Wohlgemuth R.

Great advances in tools and methodologies along the whole workflow are providing sustainable routes to a desired metabolite which can replace extractive manufacturing from endangered biological species or lengthy chemical routes from fossil-based starting materials.

Wohlgemuth R.

Phosphorus-containing metabolites cover a large molecular diversity and represent an important domain of small molecules which are highly relevant for life and represent essential interfaces between biology and chemistry, between the biological and abiotic world. The large but not unlimited amount of phosphate minerals on our planet is a key resource for living organisms on our planet, while the accumulation of phosphorus-containing waste is associated with negative effects on ecosystems. Therefore, resource-efficient and circular processes receive increasing attention from different perspectives, from local and regional levels to national and global levels. The molecular and sustainability aspects of a global phosphorus cycle have become of much interest for addressing the phosphorus biochemical flow as a high-risk planetary boundary. Knowledge of balancing the natural phosphorus cycle and the further elucidation of metabolic pathways involving phosphorus is crucial. This requires not only the development of effective new methods for practical discovery, identification, and high-information content analysis, but also for practical synthesis of phosphorus-containing metabolites, for example as standards, as substrates or products of enzymatic reactions, or for discovering novel biological functions. The purpose of this article is to review the advances which have been achieved in the synthesis and analysis of phosphorus-containing metabolites which are biologically active.

Topakas E., Boehr D., Wohlgemuth R.

The milestone of the 10th anniversary of Catalysts is a great time to reflect on past accomplishments, present progress and challenges, as well as to identify future challenges and opportunities [...]

Wohlgemuth R.

Reactions involving the transfer of phosphorus-containing groups are of key importance for maintaining life, from biological cells, tissues and organs to plants, animals, humans, ecosystems and the whole planet earth. The sustainable utilization of the nonrenewable element phosphorus is of key importance for a balanced phosphorus cycle. Significant advances have been achieved in highly selective and efficient biocatalytic phosphorylation reactions, fundamental and applied aspects of phosphorylation biocatalysts, novel phosphorylation biocatalysts, discovery methodologies and tools, analytical and synthetic applications, useful phosphoryl donors and systems for their regeneration, reaction engineering, product recovery and purification. Biocatalytic phosphorylation reactions with complete conversion therefore provide an excellent reaction platform for valuable analytical and synthetic applications.

Rietzschel E., Jayawardhane K., Zubair M., Chen G., Ullah A.

Cabadaj P., Illeová V., Lech M., Bučko M., Polakovič M.

Titova E.S.

The goal of the article is to study interconnection between bio-economy shaping, development of human capital and population health in regions of Russia. Certain indicators of population health were analyzed in federal areas and regions of the Russian Federation in the 21st century. The research showed a trend to reduction in death-rate of employable people (death number per 100.000 people). At the same time it was found that death-rate in the NorthCaucasian federal area was considerably lower in comparison with other areas and in Russia in general (by Mann – Whitney non-parametric criterion). Dynamics of population sick-rate in the Russian Federation was illustrated by key classes of illnesses in 2000–2022.  Findings of the research underline that socially important illnesses and TB among them are important for population health, which is considered as one of the most significant components of human capital that plays a principle role in the development of regional economy. Analysis of statistic data shows reliable cut in TB numbers from 2010 to 2022 in all federal areas. The authors show cyclic interdependence of bioeconomy functioning and development of human capital by provision of population health as one of possible ways. The research put forward a cyclic model of interconnection between the condition of human capital, characteristics of public health system operation and prospects of bio-economy development, which gives an opportunity to assess the potential of regional development of bio-economy.

Borowiecki P., Schmidt S.

TITOVA E.S.

Subject. The article discusses the influence of biotechnology on the development of various sectors of the economy. Objectives. The study aims at correlation of different groups of biotechnology with types of economic activity, analysis of prospects for bioeconomy development. Methods. I performed the content analysis of scientific literature, constructed Sankey diagrams. Results. The study established that many biotechnologies are applied in various sectors of the economy, including the production of food products, pharmaceuticals, and materials used for medical purposes. I developed a new approach to planning regional economic development, taking into account climatic and geographical characteristics and focused on resource conservation, which implies the creation of mechanisms for integrating biotechnology into economic activities. Conclusions. Further spread of biotechnology will contribute to the formation of competitive bioeconomy, which aligns with the national interests of Russia.

Giampietro M., Funtowicz S., Bukkens S.G.

Abstract In this paper, we show that the characteristics of complex adaptive systems support the original interpretation of the bioeconomy of Georgescu-Roegen: the current use of natural resources by industrialized societies is incompatible with the regeneration processes of ecological systems. Elaborating the concept of societal identity, using a biosemiotics reading of the social theory of Luhmann, we show that the current social identity is sustained by implausible sociotechnical imaginaries, including the European Union’s interpretation of the bioeconomy as a panacea for green growth. We argue that the current widespread perception of polycrisis is a sign that, on the tangible side of biosemiotic process, social practices urgently need change. On the notional side, however, society is (still) incapable of relinquishing the set of sociotechnical imaginaries grounded in the American and Cartesian dreams (the promethean ideology) firmly locked in its collective memory. This incongruity has produced information disorder in the sustainability discourse. We conclude that the EU endorsement of the concept of the circular (bio)economy as a strategy for perpetual economic growth decoupled from resource use represents a desperate attempt to maintain the status quo through the endorsement of an integrated set of noble lies.

Wu F., Yu S., He Y., Gao Z., Zhao T.

Abstract Bound states in the continuum (BIC) present a novel avenue for advancing high-quality factor metasurfaces, promising in high-performance lasers, sensors, and nonlinear optical devices at the nanoscale. Currently, sensors designed based on BIC have achieved good sensing performance. However, the functionality of current metasurface sensors is relatively singular, rendering them less chance in complex sensing scenarios. Specifically, taking a bio-enzyme metasurface sensor as an example, since different bio-enzymes have different optimal reaction temperatures, it is mostly inescapable to design multiple metasurface sensors for different bio-enzyme detection. In this paper, we developed a multifunctional sensor that can adapt to different reaction temperatures of bio-enzymes, meeting the requirements of multiple scenarios. The proposed metasurface consists of two elliptical cylinders, which can excite a high-Q quasi-BIC resonance by changing their rotation angles. By introducing VO2 film, external ambient temperature can effectively manipulate the transmission modulation depth and quasi-BIC. Simulation results show the maximum relative modulation depth of the metasurface can reach 296%. When combined with bio-enzymes, the metasurface serves as a refractive index sensor with a sensitivity as high as 370 nm RIU−1 at 30 °C and 80 °C. Our work provides insights for the design of highly integrated and tunable devices in the future.

Heinz F., Meinert H., Somvilla I., Menke M.J., Dörr M., Bayer T., Bornscheuer U.

AbstractThe methylation of small molecules is of immense value to various chemical industries. Since chemical alkylation requires rather unselective and harsh reaction conditions, sustainable biocatalytic approaches are highly desired. Methyltransferases, particularly N‐methyltransferases (NMTs), facilitate the selective introduction of methyl (and other alkyl) groups under mild conditions in aqueous solution and are a promising alternative to chemical synthesis. In this work, we expanded the toolbox of NMTs through the bioinformatic‐assisted mining of databases and the high‐throughput characterization of novel NMTs by a fluorescence‐based assay. The latter can assess enzyme activity in cell lysates, independent of the investigated substrate, and was used to guide the engineering of newly identified NMTs. Mutants, exhibiting up to 8‐fold improved selective methylation of (non‐)natural N‐heterocyclic drug precursors, were identified and promise great potential for synthetic applications.

Israr M., Padhi S.K., Zhou Y., Wu S.

AbstractAmino acid transaminases (ATs) have garnered considerable attention in recent years as promising biocatalysts for the synthesis of high‐value chiral chemicals, including both natural and non‐canonical amino acids. These enzymes catalyze the transfer of amino groups from amino acids to keto acids, playing a pivotal role in various biological processes and industrial applications. Characterized by their high turnover rates, remarkable enantioselectivity, and broad substrate specificity, ATs exhibit exceptional versatility and potential. This review presents a comprehensive overview of the classification, reaction mechanisms, and activity assays of ATs. More crucially, we delve into the recent advancements in protein engineering of ATs through directed evolution and rational/semi‐rational design strategies, which have been instrumental in addressing limitations such as low catalytic efficiency and stability. Furthermore, we survey the recent synthetic applications of ATs in the production of aliphatic and aromatic amino acids, highlighting smart amino donors and coupling methods that effectively shift the equilibrium of transamination reactions, as well as enzyme cascades that further expand the scope of reactions. By bridging gaps in research on ATs, this review aims to provide valuable insights and guidance for future developments in the field of biocatalysis, ultimately fostering their continued utilization and advancement.

Kamusingize D., Ronner E., Taulya G., de Vos R., Namanya P., Kubiriba J., Descheemaeker K.

Koo Y.S., Chen A.X., Tay C.Y., Wang V.Y., See J.Y., Lim Y.H., Tay D.W.

Stracke C., Meyer B.H., DeRose S.A., Ferrandi E.E., Kublanov I., Isupov M.N., Harmer N., Monti D., Littlechild J., Mueller F., Snoep J.L., Braesen C., Siebers B.

AbstractExtremolytes – unique compatible solutes produced by extremophiles - protect biological structures like membranes, proteins, and DNA under extreme conditions, including extremes of temperature and osmotic stress. These compounds hold significant potential for applications in pharmaceuticals, healthcare, cosmetics, and life sciences. However, despite their promise, only a few extremolytes, such as ectoine and hydroxyectoine, are commercially established, primarily due to the lack of efficient production strategies for other compounds.Cyclic 2,3-diphosphoglycerate (cDPG), a unique metabolite found in certain hyperthermophilic methanogenic Archaea, plays a key role in thermoprotection and is synthesized from 2-phosphoglycerate (2PG) through a two-step enzymatic process involving 2-phosphoglycerate kinase (2PGK) and cyclic-2,3-diphosphoglycerate synthetase (cDPGS). In this study, we present the development of an efficientin vitroenzymatic approach for the production of cDPG directly from 2,3-diphosphoglycerate (2,3DPG), leveraging the activity of the cDPGS fromMethanothermus fervidus(MfcDPGS).We optimized the heterologous production ofMfcDPGS inEscherichia coliby refining codon usage and expression conditions. The purification process was significantly streamlined through an optimized heat precipitation step, coupled with effective stabilization ofMfcDPGS for both usage and storage by incorporating KCl, Mg2+, reducing agents and omission of an affinity tag. The recombinantMfcDPGS showed aVmaxof 38.2 U mg-1, withKMvalues of 1.52 mM for 2,3DPG and 0.55 mM for ATP. The enzyme efficiently catalyzed the complete conversion of 2,3DPG to cDPG. Remarkably, even at a scale of 100 mM, it achieved full conversion of 37.6 mg of 2,3DPG to cDPG within 180 minutes, using just 0.5 U of recombinantMfcDPGS at 55°C. These results highlight thatMfcDPGS can be easily produced, rapidly purified, and sufficiently stabilized while delivering excellent conversion efficiency for cDPG synthesis as value-added product. Additionally, a kinetic model forMfcDPGS activity was developed, providing a crucial tool to simulate and scale up cDPG production for industrial applications. This streamlined process offers significant advantages for the scalable synthesis of cDPG, paving the way for further biochemical and industrial applications of this extremolyte.

Nicolas M., Gaelings N., Wiesenthal J., Graf von Westarp W., Pehlivanlar B., Pischinger S., Jupke A., Klankermayer J., Rother D.

AbstractIn the catalytic conversion of renewable raw materials, it is essential to adapt the reaction media to match the complexity of substrates. Recently, integrated bio‐ and organometallic catalysis processes have emerged; however, only a few operate in purely organic solvents, which would be advantageous for more energy‐efficient processes. In this study, we present a process using one enzymatic step and two organometallic steps to produce the cyclic acetals 4,5‐dipropyl‐1,3‐dioxolane and 4,5‐dibutyl‐1,3‐dioxolane in a single organic solvent. The enzymatic step, in which a lyase is used, starts from the aldehyde, butanal orpentanal, and forms the 2‐hydroxy ketones butyroin or valeroin, respectively. Subsequently, two organometallic steps were carried out sequentially in one reaction vessel. In a first step, the 2‐hydroxy ketones are hydrogenated to 4,5‐octanediol and 5,6‐decanediol and in the second step the dioxolanes are formed by using hydrogen and carbon dioxide. Either formic acid or polyoxymethylene was used as an alternative carbon source to CO2, which allowed considerable raw material flexibility. Since these dioxolanes are being investigated as additives in biofuel blends, the derived cetane number of the synthesized compounds was measured in addition to the viscosity and density. The cetane numbers determined suggest that the produced dioxolanes could be used as additives in fuel blends.

Papadopoulou C., Foutri A., Martinidis G., Kalea T., Fallas Y.

The development of the bioeconomy in the European Union is promoted through various policies. In Greece, however, there is a paucity of research on bioeconomy issues and policies at both the national and regional levels. This study systematically examines the feasibility of developing a bioeconomy blueprint within the context of a geographically isolated and mountainous region. By employing an integrated strategic framework combining sustainable resource management, innovation and participatory governance, the proposed framework emphasizes the transition from conventional, unsustainable economic practices to a contemporary development paradigm underpinned by the tenets of the circular economy and the utilization of local resources. A central tenet of the proposed framework is the enhancement of collaborative endeavors among local stakeholders, academic institutions, and business entities, with the overarching objective being the promotion of cutting-edge technologies and the economic diversification of the region. Concurrently, emphasis is placed on the necessity to establish conducive policies, regulatory frameworks, and financial mechanisms that will facilitate the development of sustainable industries and mitigate the environmental impact. The text emphasizes the importance of human resources development through educational and training programs, ensuring adaptability to the demands of the emerging bioeconomy. The study concludes that, despite the inherent difficulties arising from geographical isolation and limited access to resources, the region has the potential for sustainable development. The region’s capacity for sustainable development is contingent upon the implementation of suitable strategies and the mobilization of investment, which will be instrumental in the establishment of a robust and environmentally sustainable economic model.

Genz F., Friedrich F., Lönarz C., Einsle O., Jung M., Müller M., Fessner N.D.

Sheldon R.A.

The pressing need to mitigate climate change and drastically reduce environmental pollution and loss of biodiversity has precipitated a so-called energy transition aimed at the decarbonization of energy and defossilization of the chemical industry. The goal is a carbon-neutral (net-zero) society driven by sustainable energy and a circular bio-based economy relying on renewable biomass as the raw material. It will involve the use of green carbon, defined as carbon derived from terrestrial or aquatic biomass or organic waste, including carbon dioxide and methane emissions. It will also necessitate the accompanying use of green hydrogen that is generated by electrolysis of water using a sustainable source of energy, e.g. solar, wind or nuclear. Ninety per cent of the industrial chemicals produced in oil refineries are industrial monomers that constitute the precursors of a large variety of polymers, many of which are plastics. Primary examples of the latter are polyolefins such as polyethylene, polypropylene, polyvinyl chloride and polystyrene. Polyolefins are extremely difficult to recycle back to the olefin monomers and discarded polyolefin plastics generally end up as the plastic waste that is responsible for the degradation of our natural habitat. By contrast, waste biomass, such as the lignocellulose contained in forestry residues and agricultural waste, constitutes a renewable feedstock for the sustainable production of industrial monomers and the corresponding polymers. The latter could be the same polyolefins that are currently produced in oil refineries but a more attractive long-term alternative is to produce polyesters and polyamides that can be recycled back to the original monomers: a paradigm shift to a truly bio-based circular economy on the road to a net-zero chemical industry. This article is part of the discussion meeting issue ‘Green carbon for the chemical industry of the future’.

Hua Z., Wu Q., Yang Y., Liu S., Jennifer T.G., Zhao D., Fang Y.

Zheng J., Lin X., Xu H., Sohail M., Chen L., Zhang X.

Glycosaminoglycans (GAGs) are a family of structurally complex heteropolysaccharides that play pivotal roles in biological functions, including the regulation of cell proliferation, enzyme inhibition, and activation of growth factor receptors. Therefore, the synthesis of GAGs is a hot research topic in drug development. The enzymatic synthesis of GAGs has received widespread attention due to their eco-friendly nature, high regioselectivity, and stereoselectivity. The enhancement of the enzymatic synthesis process is the key to its industrial applications. In this review, we overviewed the construction of more efficient in vitro biomimetic synthesis systems of glycosaminoglycans and presented the different strategies to improve enzyme catalysis, including the combination of chemical and enzymatic methods, solid-phase synthesis, and protein engineering to solve the problems of enzyme stability, separation and purification of the product, preparation of structurally defined sugar chains, etc., and discussed the challenges and opportunities in large-scale green synthesis of GAGs.

Bayer T., Palm G.J., Berndt L., Meinert H., Branson Y., Schmidt L., Cziegler C., Somvilla I., Zurr C., Graf L.G., Janke U., Badenhorst C.P., König S., Delcea M., Garscha U., et. al.

AbstractWhile plastics like polyethylene terephthalate can already be degraded efficiently by the activity of hydrolases, other synthetic polymers like polyurethanes (PUs) and polyamides (PAs) largely resist biodegradation. In this study, we solved the first crystal structure of the metagenomic urethanase UMG‐SP‐1, identified highly flexible loop regions to comprise active site residues, and targeted a total of 20 potential hot spots by site‐saturation mutagenesis. Engineering campaigns yielded variants with single mutations, exhibiting almost 3‐ and 8‐fold improved activity against highly stable N‐aryl urethane and amide bonds, respectively. Furthermore, we demonstrated the release of the corresponding monomers from a thermoplastic polyester‐PU and a PA (nylon 6) by the activity of a single, metagenome‐derived urethanase after short incubation times. Thereby, we expanded the hydrolysis profile of UMG‐SP‐1 beyond the reported low‐molecular weight carbamates. Together, these findings promise advanced strategies for the bio‐based degradation and recycling of plastic materials and waste, aiding efforts to establish a circular economy for synthetic polymers.

Kissman E.N., Sosa M.B., Millar D.C., Koleski E.J., Thevasundaram K., Chang M.C.

Living systems contain a vast network of metabolic reactions, providing a wealth of enzymes and cells as potential biocatalysts for chemical processes. The properties of protein and cell biocatalysts—high selectivity, the ability to control reaction sequence and operation in environmentally benign conditions—offer approaches to produce molecules at high efficiency while lowering the cost and environmental impact of industrial chemistry. Furthermore, biocatalysis offers the opportunity to generate chemical structures and functions that may be inaccessible to chemical synthesis. Here we consider developments in enzymes, biosynthetic pathways and cellular engineering that enable their use in catalysis for new chemistry and beyond. This Review considers developments in enzymes, biosynthetic pathways and cellular engineering that enable their use in catalysis for new chemistry and beyond.

Etit D., Meramo S., Ögmundarson Ó., Jensen M.K., Sukumara S.

The impact-intensive and rapidly growing pharmaceutical industry must ensure its sustainability. This study reveals that environmental sustainability assessments have been conducted for only around 0.2% of pharmaceuticals, environmental impacts have significant variations among the assessed products, and different impact categories have not been consistently studied. Highly varied impacts require assessing more products to understand the industry's sustainability status. Reporting all impact categories will be crucial, especially when comparing production technologies. Biological production of (semi)synthetic pharmaceuticals could reduce their environmental costs, though the high impacts of biologically produced monoclonal antibodies should also be optimized. Considering the sustainability potential of biopharmaceuticals from economic, environmental, and social perspectives, collaboratively guiding their immense market growth would lead to the industry's sustainability transition.

McDonald M.A., Koscher B.A., Canty R.B., Jensen K.F.

Reaction optimization and characterization depend on reliable measures of reaction yield, often measured by high-performance liquid chromatography (HPLC).

Wohlgemuth R.

Shaw W.J., Kidder M.K., Bare S.R., Delferro M., Morris J.R., Toma F.M., Senanayake S.D., Autrey T., Biddinger E.J., Boettcher S., Bowden M.E., Britt P.F., Brown R.C., Bullock R.M., Chen J.G., et. al.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets. To achieve net-zero carbon emissions, we must close the carbon cycle for industries that are difficult to electrify. Developing the needed science to provide carbon alternatives and non-fossil carbon will accelerate advances towards defossilization.

Guntelmann T., Dietz K., Gröger H.

A biocatalytic cascade synthesis of cis-(+)-12-OPDA at 5–20 gL−1 substrate loading was developed, leading to excellent conversion, chemical purity (>99%), enantio- and diastereomeric excess (>99% ee, 96% de) as well as neglectable side-product (<1%).

Yi X., Kleinbeck F., Ching C., Boghospor L., Gomes S., Alvizo O., Allmendinger T., Fell J., Subramanian N., Li M., Garcia R., Riggins J., Entwistle D., Richter Y., Gschwend D., et. al.

Thorpe T.W., Marshall J.R., Turner N.J.

Tiedemann S., Neuburger J.E., Gazizova A., von Langermann J.

AbstractTransaminases are valuable catalysts in the synthesis of chiral amines. However, secondary techniques are typically required to shift the reaction equilibrium to the product side. This study focuses on the in situ product crystallization, specifically at preparative synthetic scale as a non‐synthetic tool for a selection of aromatic and aliphatic substrates using the transaminase from Silicibacter pomeroyi. Herein the technique is implemented in a simplified manner to facilitate in situ product removal and downstream‐processing in a combined crystallization step. After a series of optimizations, product concentrations of >0.9 mol/L and >99 % e.e. (S) were obtained implementing a repetitive batch reaction approach using a universal carboxylate as anion.

Cheung-Lee W.L., Kolev J.N., McIntosh J.A., Gil A.A., Pan W., Xiao L., Velásquez J.E., Gangam R., Winston M.S., Li S., Abe K., Alwedi E., Dance Z.E., Fan H., Hiraga K., et. al.

AbstractBiocatalytic oxidations are an emerging technology for selective C−H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non‐heme iron and α‐ketoglutarate‐dependent dioxygenase for the direct stereo‐ and regio‐selective hydroxylation of a non‐native fluoroindanone en route to the oncology treatment belzutifan, replacing a five‐step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high‐yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan.

Noor E., Liebermeister W.

How to optimize the allocation of enzymes in metabolic pathways has been a topic of study for many decades. Although the general problem is complex and nonlinear, we have previously shown that it can be solved by convex optimization. In this paper, we focus on unbranched metabolic pathways with simplified enzymatic rate laws and derive analytic solutions to the optimization problem. We revisit existing solutions based on the limit of mass-action rate laws and present new solutions for other rate laws. Furthermore, we revisit a known relationship between flux control coefficients and enzyme abundances in optimal metabolic states. We generalize this relationship to models with density constraints on enzymes and metabolites, and present a new local relationship between optimal reaction elasticities and enzyme amounts. Finally, we apply our theory to derive simple kinetics-based formulae for protein allocation during bacterial growth.