Enzymes are protein biocatalysts that operate under aqueous and mild conditions, intrinsically aligning with the principles of green and sustainable chemistry. This review highlights recent water-compatible and site-selective protein modification methods that target specific amino acid residues or protein termini. We also describe complementary two-step strategies that combine chemical or biotechnological techniques. We then summarize applications that regulate enzyme function, enable enzyme immobilization for reuse, and install new catalytic activities into protein scaffolds. Finally, we discuss future perspectives in this field, where integrating site-selective protein modifications with computational methods will accelerate advances in protein bioconjugation and artificial enzyme design, thereby expanding their impact across organic synthesis, medicinal chemistry, and materials science in both research and industrial settings.
Machine learning (ML) has gained considerable attention across scientific fields, including organic synthesis and biocatalysis. With the potential to achieve more resource-efficient and sustainable reaction development through reducing experimental burden, the motivation to embrace ML to support decision-making is high. To enhance ML's utility, the dataset and ML approach need to be designed to align well with the goal of a given experiment. This article reviews recent advances in ML for small molecule methods and biocatalysis by categorizing the types of problems in organic synthesis. By comparing the forefront of both fields, we identify opportunities, such as dataset design strategies, as well as research directions to further facilitate the incorporation of ML in both small molecule reactions and biocatalysis.
Meeting rising global protein demand within planetary boundaries necessitates a shift towards more resilient, circular production models. Fermentation of agri-food side streams offers a promising land-light alternative with possible economic benefits but must overcome significant barriers such as feedstock variability, distributed supply chains, and safety. This article proposes Fermentelligence (AI-optimised fermentation) as the critical enabler to unlock this potential. The article presents how machine learning and digital technologies can manage system-wide variance by highlighting key recent work in this area; including optimising complex feedstock blends, real-time process control, and economic and sustainability-aware decision-making. Furthermore, it highlights the strategic importance of decentralised regional hubs and the retrofitting of legacy assets, such as breweries and wineries, to lower capital costs. Finally, the article outlines a de-risking roadmap emphasising open data ecosystems, food safety evidence, and pilot demonstrations to accelerate the transition from linear agriculture to a flexible, AI-optimised circular bioeconomy.
This critical review highlights recent advances in the catalytic continuous flow synthesis of γ-valerolactone from levulinic acid, furfural, or biomass derivatives using catalytic hydrogenation with hydrogen H2 and catalytic transfer hydrogenation with i-propanol. It also covers the catalytic continuous flow production of various bio-based chemicals, including valeric acid, butenes, and buta-1,3-diene.
Sugar fatty acid esters (SFAEs) are promising bio-based surfactants due to their biodegradability, low toxicity, versatile physicochemical properties and applications. Advances in lipase-catalysed processes facilitated their production. In parallel, recent research has expanded toward structurally diverse, rare or underutilised sugars to tailor interfacial behaviour, bioactivity, and application-specific performance.However, functional diversification has progressed faster than the integration of sustainable feedstocks and process design. Rare and underutilised sugars are often combined with activated acyl donors or process configurations prioritising reaction efficiency over sustainability. Consequently, many systems remain better suited for rapid synthesis and structure–function studies than for scalable, circular production.This perspective examines recent advances (2024–2026) in lipase-catalysed SFAE synthesis, arguing for the potential of rare sugars to bridge biomass valorisation with advanced functionality, while recognising that integration remains a research agenda rather than an established reality, and outlines the process-level strategies needed to realise it.
Waste-to-energy (WtE) systems are increasingly studies due to rising waste generation, limited landfill capacity, and demand for low carbon energy. Unlike single output systems, multigeneration systems convert biomass or waste into multiple products electricity, heat, cooling, hydrogen and biofuels. This review summarises recent techno-economic and environmental assessments of such systems focusing on integrated waste- and biomass-to-energy pathways. The literature shows a shift from simple waste-to-power systems towards highly integrated configurations combining gasification, combustion, pyrolysis and anaerobic digestions combined with bottoming cycles, fuel cells, refrigeration systems, fuel production and carbon capture. These systems improve resource utilisation and wate heat recovery but increase complexity and cost. Overall, multigeneration systems offer strong potential for improving efficiency and sustainability through process integration and product diversification. Future work should prioritise dynamic modelling under variable waste conditions, standardised techno-economic assumptions and improved integration of circular economy and supply chain considerations to ensure scalability and deployment.
Organoboron chemistry plays a central role in modern organic synthesis with direct impact in academy and pharmaceutical industry, where the Suzuki–Miyaura stands out as the most popular reaction. Considering the increasing demand for environmentally more sustainable practices, the Suzuki–Miyaura reaction has evolved and considerable effort has been devoted to transitioning this reaction from traditional organic solvents to water and reducing the amount of palladium used. On the other hand, little attention has been paid to the development of more sustainable methodologies for the synthesis of the requisite organoboron starting materials. This review highlights advances in the development of organoboron chemistry in water, focusing on three key areas: (i) borylation of aryldiazonium salts, (ii) Miyaura borylation, and (iii) emerging strategies for hydroboration of alkynes. These approaches demonstrate that water can serve not only as a benign solvent but also as a unique reaction medium that enables new reactivity and improved sustainability.
Biomass-to-renewable fuel conversion is increasingly recognised as a cornerstone of global decarbonisation strategies. However, its large-scale deployment remains constrained by feedstock heterogeneity, catalyst cost, and inefficient downstream processing. Recent advances in biomass-derived heterogeneous catalysts offer a compelling pathway to address these bottlenecks by enabling cost-effective, recyclable, and structurally tunable catalytic systems. Emerging biochar-derived materials, including metal-functionalised acidic catalysts, metal–organic frameworks (MOFs), single-atom catalysts (SACs), and tunable bifunctional acid-base catalysts, which demonstrate enhanced activity, selectivity, and tolerance towards complex biomass feedstocks. Concurrently, innovations in hierarchical structuring, defect engineering, and heteroatom doping enable precise control over catalytic interfaces and reaction pathways. Beyond catalyst design, the integration of these systems within circular biorefinery frameworks and process intensification strategies is gaining traction to produce sustainable drop-in fuels. This work highlights these recent breakthroughs and outlines key directions toward the development of robust, scalable, and economically viable technologies for next-generation renewable biofuel production.
Oxidizing enzymes are indispensable in organic synthesis, enabling transformations with unparalleled selectivity under mild conditions. This review highlights recent advances in the discovery, engineering, and synthetic application of four key oxidoreductase classes: oxygenases, dehydrogenases, oxidases, and peroxidases. We discuss strategies to overcome native enzyme limitations—including protein engineering, ancestral sequence reconstruction, and chemical mechanism-guided repurposing—and showcase their integration into multi-enzyme cascades and chemo-enzymatic platforms. By leveraging computational design and hybrid photochemical/electrochemical systems, enzymatic oxidation is poised to address long-standing challenges in C–H functionalization and offer versatile, scalable routes to high-value chemicals.
Among alternatives to the large volumes of organic solvents commonly employed in organic synthesis, water is particularly appealing owing to its safety, non-toxicity, and abundance. Even more so when water is used in combination with a precise ratio of organic solvent, the resulting azeotrope can be considered a strategic tool for transitioning toward a more responsible and sustainable chemical production. Recent literature discussed herein highlights the role of aqueous azeotropes in the production of chemicals and materials, as well as in the design of waste–minimization processes and waste valorization approaches. Indeed, azeotropic distillation offers several advantages, including reduced energy costs, improved synthetic protocols, and high yield while minimizing by-product formation, thereby facilitating purification. Moreover, the use of azeotropes facilitates the recovery and reuse of reaction media and unreacted materials, thereby minimizing waste.
Torrefaction is increasingly recognised as a promising thermochemical pre-treatment for upgrading low-grade biomass into coal-like solid biofuels with improved energy density, hydrophobicity, grindability, and storage stability. This review focuses on recent advances in torrefaction processes, fuel-property enhancement, process optimisation, and scale-up. Conventional dry torrefaction remains the most established route; at the same time, emerging methods such as hydrothermal carbonisation, oxidative torrefaction and superheated steam offer opportunities to improve feedstock flexibility, heat transfer, reaction kinetics, and product quality. Torrefaction generally increases higher heating value, energy densification, and fixed carbon content, and reduces moisture and volatile matter; however, these benefits are often accompanied by reduced mass yield and ash concentration. Recent optimisation studies, using response surface methodology and analysis of variance, have improved understanding of parameter interactions and feedstock-specific operating windows. Despite this progress, large-scale deployment remains limited by feedstock variability, non-uniform heat transfer, atmosphere control, and continuous feeding challenges.
In recent times, electro-organic synthesis (or e-synthesis) has gained increasing recognition for its use of electrons and protons as redox agents, demonstrating its potential as a powerful technique for synthesising complex molecules. This approach is environmentally friendly, sustainable, and scalable. In this review, we briefly discussed the core electrochemical methodology, history, electrodes, electrolytes, solvents, micellar-catalysis, green matrices, and their sustainability. Additionally, we provided a brief discussion on the advantages and disadvantages of electro-organic synthesis, in comparison to other conventional methods, in the context of green metrics. This review aims to introduce researchers to the adoption of electrosynthesis as an environmentally friendly, accurate, and cost-effective approach for creating complex organic frameworks.
The replacement of organic solvents with water is a key objective in the development of more sustainable chemical manufacturing. Aqueous micellar systems, employing surfactants as enabling additives, have emerged as effective platforms for promoting organic transformations in water. However, these systems often form biphasic mixtures or slurries that restrict mass transfer and reduce reaction efficiency, particularly during scale-up. Continuous flow technology provides practical solutions to these challenges by improving mixing and mass transport while allowing precise control over reaction conditions. This review surveys recent developments demonstrating how flow chemistry facilitates efficient synthesis in water as reaction medium, thereby advancing the implementation of greener and more sustainable chemical processes.
Photochemical synthesis enables bond construction with exceptional spatiotemporal control under mild and energy-efficient conditions. When performed in water, these advantages are amplified, offering a genuinely sustainable reaction platform. Although aqueous media have traditionally constrained photochemical scope, recent advances in reaction engineering, catalytic design, and reactor technologies have rapidly expanded accessible transformations. This review highlights progress in micellar photocatalysis, aquaphotocatalysis, and photoenzymatic/ biohybrid systems, illustrating how water actively shapes reactivity through polarity, interfacial organization, and proximity effects. Together with developments in flow chemistry and automation, these approaches position aqueous photochemistry as a versatile and scalable paradigm for future green synthesis.
This review surveys recent advances in oxidative biocatalysis, expanded enzyme reactivity, scope and practical utility. We focus on cytochrome P450 monooxygenases, unspecific peroxygenases and non-heme iron-dependent enzymes, emphasizing breakthroughs in small-molecule functionalization, late-stage diversification of natural products and reactions beyond oxygen incorporation. This review showcases how protein engineering has enabled new-to-nature transformations, improved selectivity, scalability and robustness, and reduced reliance on costly cofactors. Collectively, these developments demonstrate the growing impact of oxidative biocatalysts in sustainable synthesis, drug discovery and pharmaceutical development, while underscoring remaining challenges in linking sequence space to chemical reactivity.
Electrochemical synthesis using water, as a green and sustainable chemical synthesis method, has garnered extensive attention in recent years. This approach utilizes water as both solvent and reactant, reducing the use of organic solvents and avoiding environmental pollution. As a key technology for realizing green chemistry, electrochemical synthesis using water has undergone a paradigm shift from "replacing organic solvents with water" to "water acting as an active reactant" in recent years. This review summarizes the significant advances in the field of electrochemical synthesis using water over the past two years, with a focus on the research progress of water as a solvent and reactant in as the solubility of hydrophobic substrates and the competition from hydrogen/oxygen evolution reactions, are discussed along with future perspectives for industrial applications.
powerful approach for performing valuable cross-couplings, such as C -C and C-N in water, while addressing catalyst solubilize and concentrate hydrophobic substrates, while metal-embedded porous supports provide site isolation, robustness, and recyclability. Combining these, one can generate in situ solid-liquid interfaces that enhance substrate delivery, stabilize intermediates, and suppress leaching or aggregation, addressing key challenges in catalyst life-cycle management and regulatory compliance.
The exploitation of renewable energy resources for energy production has been inevitable for the unremitting development of modern society. Bioenergy offers a significant perspective in this scenario for contributing to sustainable energy availability. Biomass, which is a renewable and carbon-neutral source of energy, can be converted from its various forms into gaseous, liquid, and solid fuels by adopting the established biomass conversion technologies. Specifically, thermochemical, biological, and chemical conversion processes are technologies engaged in converting biomass into various fuels. The selection of biomass feedstocks and the type of conversion processes are selected based on the obligatory end-products. The technical and energy process flowsheet, engineering design, and ultimately the economics of biomass conversion can be optimized by integrating multiple biomass conversion processes. Hence, a state-of-the-art review is presented to highlight the significance of hybrid biomass conversion technologies for enhancing the energy-efficient conversion of biomass materials. This review study is helpful in broadening the scope of selection for the biomass conversion technology and its potential integration with other biomass conversion technologies for commercial implementation and future research studies.
