Biocatalysis@TUDelft

Ene reductases known for the reduction of C═C double bonds were shown to reduce C═N bonds, thus (a) selected oximes bearing two ester groups attached to the oximo moiety were reduced to the aliphatic amine moiety, as well as (b) a nitro group and a (c) hydrazone moiety was accepted as well.

ABSTRACT

The biocatalytic reduction of oximes may offer a potential alternative route to primary amines. However, previous studies on biocatalytic oxime reduction using α-oximo-β-keto ester substrates led to an amine intermediate which spontaneously dimerized to the corresponding pyrazine. In this study, to access the primary amine, the reduction of α-oximo malonic esters catalyzed by ene-reductases (EREDs) was explored as a promiscuous activity. Thus, a panel of 14 oximes activated by two adjacent ester moieties was evaluated, employing both wild-type and engineered EREDs. The reduction of these substrates indeed led to the corresponding stable primary amine functionality. Moreover, the unprecedented ERED-catalyzed reduction of the nitro functionality of dimethyl nitromalonate and a hydrazone functionality to the corresponding amines was demonstrated. The nitro reduction is proposed to proceed via the oxime and subsequently imine intermediates in analogy to the reduction of the oxime moiety. These results highlight the synthetic potential of EREDs in the reduction of diverse nitrogenous functionalities toward valuable amine compounds.

In this study, we have structurally characterized porphyrin and porphyrin-based metal–organic framework and analyzed the efficacy of toward photoinduced antibacterial properties.

Herein, we have synthesized the commonly known protonated 5,10,15,20-tetrakis(4-pyridyl)porphyrin (compound 1) and a mixed-linker zinc-based metal–organic framework (compound 2) and evaluated their antibacterial photodynamic therapy. The crystal structure of 1 exhibits hydrogen-bonded scaffolds and engages in π-stacking interactions, whereas compound 2 is coordinated through zinc metal nodes to porphyrin and terephthalate ions, forming an interpenetrated 3D framework with a mog topology. In 2, we observed a high theoretical surface area of 2915 m² g⁻¹ calculated using a N₂ apparatus. Molecular orbital calculations confirm that the highest occupied and lowest unoccupied molecular orbitals are mainly localized on the porphyrin core, with the terephthalate linker acting as an electronic spacer. Finally, 2 exhibits an enhanced reactive oxygen species production and superior antibacterial activity compared to 1 under irradiation with red light. These performances clearly resulted in inhibition zones of 28±1 mm (MRSA) and 21±1 mm (Escherichia coli) and strong binding properties to the proteins. These findings demonstrate that 2 functions as a robust, light-activated antibacterial platform and provide a rational route for next-generation antibacterial agents.

Ultraviolet light provides particularly strong vibrational Raman optical activity (I _R -I _L ) of chiral molecules, allowing one to better distinguish peptide and protein conformations. For three model compounds, molecular dynamics and density functional theory provided excellent basis for the interpretation of experimental data and further insight, such as localization of dynamic electron density (ρ) on the amide chromophore.

The spectroscopy of ultraviolet Raman optical activity (UV ROA) promises an excellent sensitivity to peptide and protein conformation, decoupling the backbone signal from most side chains. Compared to the more usual ROA with visible light, stronger intensity and additional spatial sensitivity are expected because most of the signal comes from the amide chromophore. UV ROA experiments are scarce, and links between spectral shapes and molecular structure are rather unexplored. However, on a dedicated instrument, we could acquire spectra of three peptides and analyze them on the basis of molecular dynamics and density functional theory simulations. Radical differences were observed between the spectra obtained with the 244 and 532 nm excitations, and they could be rationalized by the simulations. Bands connected to the peptide backbone vibrations are enhanced at the shorter wavelength, due to a pre-resonance with the n-π^* and π-π^* amide transitions. Further computational experiments on the Ala₄ peptide indicate that sensitivity to the secondary structure is enhanced as well, by a combination of geometric and resonance effects. The results thus confirm the potential of UV ROA for analytical chemistry and biochemistry in terms of novel information it brings about molecular geometric and electronic structure.

Hyaluronan synthase (HAS) is a membrane-bound enzyme with specific multifunctional glycosyltransferase activity that catalyzes the alternating addition of UDP-glucuronic acid and UDP-N-acetylglucosamine to synthesize hyaluronic acid. Classification, structural characteristics, and unique biosynthesis mechanism of HAS were systematically reviewed.

Hyaluronan synthase (HAS) is a membrane-bound enzyme with specific multifunctional glycosyltransferase activity that catalyzes the alternating addition of UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylglucosamine (UDP-GlcNAc) to synthesize hyaluronic acid (HA). Widely found in microorganisms, vertebrate, and virus, HAS plays a vital role in HA biosynthesis, determining both its yield and molecular weight. Variations in sequence and catalytic properties among HASs from different sources result in HA products with distinct molecular weights and production efficiencies. High-molecular-weight HA is in high demand for biomedical applications due to its superior physiological properties. However, its industrial production faces challenges such as low yields and poor batch consistency, influenced by host strain characteristics, HAS enzyme activity, and fermentation conditions. Modulating HAS function to control HA molecular weight has become a research focus, yet its underlying mechanisms remain poorly understood due to the enzyme's small size, complex membrane-bound nature, and unresolved catalytic mechanism. This study systematically reviews the origins, phylogenetic relationships, and sequence-structural features of HAS. Using structural modeling, it explores the potential mechanisms underlying high-molecular-weight HA synthesis and highlights recent advances in HAS engineering aimed at enhancing product molecular weight. These insights provide a foundation for the rational design of HAS and the efficient biosynthesis of high-molecular-weight HA, while also contributing to a broaden understanding of multifunctional membrane protein catalysis.

This review maps how electroenzymatic cascades that couple nitrogen-cycle enzymes with C─N bond forming auxilary enzymes, powered by direct electron transfer (DET) or mediated electron transfer (MET), can upgrade N₂ and waste nitrogen streams into value-added amines, amides, amino acids, and other nitrogen-based chemicals.

ABSTRACT

The global transition toward sustainable chemical manufacturing demands technologies that leverage natural carbon and nitrogen cycles while minimizing reliance on sacrificial reagents and fossil resources. These biogeochemical cycles are fundamental to life, and enzymes catalyze many of their key transformations. Bioelectrochemical, specifically electroenzymatic, systems offer a promising route to sustainable synthesis by enabling selective redox transformations powered by electricity. However, whereas carbon-cycle enzymes are now well established in bioelectrochemical synthesis, enzymes from the nitrogen cycle remain comparatively underexplored. Moreover, the nitrogen cycle alone does not access many value-added nitrogen-containing products, which require additional C-N bond formation and organic functionalization steps. In this review, we survey electroenzymatic systems that not only produce ammonia but also upgrade inorganic nitrogen into higher-value chemicals. We highlight single enzyme systems and multi-enzyme cascades that combine nitrogen-cycle enzymes with auxiliary biocatalysts such as amine dehydrogenases, transaminases, oxidoreductases, and nitrile hydratases to generate amines, amides, amino acids, hydrazine derivatives, and other nitrogen-containing organic compounds. Despite recent progress, only a few studies report the electroenzymatic synthesis of value-added nitrogen products. We therefore identify the key scientific and engineering challenges, outline the advances needed in enzyme-electrode interfaces and cascade design, and argue that electroenzymatic nitrogen upgrading is a promising yet underdeveloped approach for future sustainable manufacturing of nitrogen-based chemicals.

The methylotrophic yeast, Ogataea methanolica uniquely harbours two alcohol oxidase (AOD) isozymes, Mod1p and Mod2p, which exhibit distinct kinetic properties and are differentially regulated by methanol and oxygen availability, enabling metabolic adaptation to fluctuating environments. Here, we report high-resolution cryogenic electron microscopy structures of the Mod1p and Mod2p homooctamers at 1.9 Å and 2.7 Å resolution, respectively.

ABSTRACT

Ogataea methanolica is a methylotrophic yeast that can produce diverse recombinant proteins using methanol as the sole carbon and energy source. Unlike most yeast species, which possess a single alcohol oxidase, O. methanolica encodes two isoenzymes, Mod1p and Mod2p. This study examines the structural and functional differences between Mod1p and Mod2p homooctamers. Both enzymes were purified from MOD-disrupted strains and analysed using cryogenic electron microscopy, achieving resolutions of 1.9 and 2.7 Å for Mod1p and Mod2p, respectively. The two isozymes assemble as tetramers of dimers stabilized by extensive intersubunit interactions, largely mediated by protruding loop regions and C-terminal extensions. Despite overall structural similarities, Mod1p and Mod2p exhibit subtle differences in surface charge distribution and sequence composition within the FAD-binding domain. These variations correlate with distinct cofactor preferences, with Mod1p binding arabityl FAD and Mod2p binding canonical FAD. Thin-section electron microscopy further revealed that Mod1p and Mod2p form both homomeric and hybrid octamers that assemble into peroxisomal crystalloids essential for methanol metabolism. Collectively, our findings provide mechanistic insight into alcohol oxidase diversity in methylotrophic yeasts, advancing our understanding of methanol utilization and its applications in biotechnology.

Biosynthesis of [~]3000 monoterpenoid indole alkaloids (MIAs) including the anticancer drug vinblastine involve the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine {beta}-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. Here we discover VinBLAST, a cinnamyl alcohol dehydrogenase repurposed as a scaffold for efficient processing of this labile intermediate. VinBLAST physically mediates SGD and GS interaction in the nucleus and allosterically enhances GS catalytic efficiency. VinBLAST homologs from diverse plant families enhance biosynthesis of several representative MIAs, with the production of catharanthine increased to [~]160 mg l-1 in yeast, nearly 1000-fold higher than previous studies. Our discovery provides the missing link in organizing MIA biosynthesis and enables scalable bioproduction of geissoschizine-derived therapeutics.

Expanding the genetic code to enable the selective and specific incorporation of non-canonical monomers (ncMs), beyond -L amino acids with variant sidechains, is a key outstanding challenge. Here we discover orthogonal aminoacyl-tRNA synthetases that selectively and specifically acylate their cognate orthogonal tRNA in vivo with eleven new ncMs spanning five different chemical classes: ,-disubstituted-amino acids, malonic acids, carboxylic acids, {beta}2-amino acids and N-cyclic amino acids. We demonstrate that co-translational incorporation of ,-disubstituted-amino acids, {beta}2-amino acids, {beta}3-amino acids and N-cyclic amino acids is strongly dependent on the codons either side of the codon used to direct ncM incorporation, with several ncMs incorporated at less than 1% of sequence contexts. We evolve orthogonal tRNAs that enable the incorporation of previously unincorporated ncMs, enable the incorporation of ncMs at >95% of sequence contexts and, increase the incorporation efficiency at challenging sequence contexts up to 40-fold. We demonstrate the encoded cellular synthesis of proteins and macrocycles containing ncMs and, explicitly demonstrate that our evolved tRNAs provide direct access to a wider range of genetically encoded macrocyclic sequences containing ncMs. Our results provide a foundation for composing, discovering and manufacturing proteins and peptides with functions augmented by ncMs.

Communications Chemistry, Published online: 18 April 2026; doi:10.1038/s42004-026-02033-3

Selective protein functionalization remains difficult to achieve through conventional molecular biology approaches. Here, the authors summarize recent advances in chemical approaches to protein engineering and highlight their emerging applications in catalysis, functional studies, and therapeutic development.

YJR096w and YDL124w from S. cerevisiae showed moderate enantioselectivity toward ethyl 3,3,3-trifluoro-2-oxopropanoate, which was elucidated by homology modeling and improved via semirational engineering. Mutants YJR096w-L49Y/D275H and YDL124w-T26G achieved excellent selectivity (99.9% R, 97.6% S). With BaGDH-based NADPH regeneration, they enabled efficient chiral ethyl 3,3,3-trifluoro-2-hydroxypropanoate production, offering an effective, green strategy for asymmetric biocatalysis.

Ethyl 3,3,3-trifluoro-2-hydroxypropanoate (TFLAEt) is an important multifunctional intermediate, and the asymmetric reduction of its corresponding fluorinated keto ester, ethyl 3,3,3-trifluoro-2-oxopropanoate (TFPyEt), to generate chiral TFLAEt represents a valuable yet challenging task in biocatalysis. In this study, several aldo–keto reductases (AKRs) from Saccharomyces cerevisiae were cloned and heterologously expressed in Escherichia coli. Their reductase activities toward TFPyEt were evaluated, and YJR096w and YDL124w exhibited moderate R-selectivity (72.6% ee) and S-selectivity (82.8% ee), respectively. Homology modeling and molecular docking with TFPyEt and NADPH were conducted to elucidate the molecular basis of their enantioselectivity. Through semi-rational engineering, two mutants—YJR096w-L49Y/D275H and YDL124w-T26G—were obtained, exhibiting excellent enantioselectivity with enantiomeric excess (ee) values of 99.9% (R) and 97.6% (S), respectively, for the reduction of TFPyEt. An NADPH regeneration system was constructed using glucose dehydrogenase (BaGDH) from Bacillus amyloliquefaciens, enabling the efficient production of chiral TFLAEt from TFPyEt under optimized biocatalytic conditions using the two mutants. This work presents an effective strategy for enhancing the enantioselectivity of native biocatalysts and provides valuable insights into the development of novel green catalysts for asymmetric transformations.

This work introduces the concept of pseudoglucosinolates (psGSLs) and reports the synthesis and evaluation of nitroreductase-responsive psGSLs. These compounds represent a complementary prodrug strategy to natural glucosinolates (GSLs) for the controlled release of isothiocyanates (ITCs), enabling bio-responsive protein labeling, as demonstrated in living C. elegans.

ABSTRACT

Glucosinolates (GSLs) are plant secondary metabolites that release bioactive isothiocyanates (ITCs) upon myrosinase-mediated activation. While ITCs display diverse antimicrobial and chemoprotective activities, their application is limited by dependence on myrosinase and intrinsic hydrolytic instability. Here, we introduce pseudoglucosinolates (psGSLs), a synthetic platform that mimics the natural GSL activation mechanism but replaces the thioglucosidic trigger with an enzyme-responsive para-aminobenzylthiol motif. Using nitroreductase (NfsB) as a noncanonical activating enzyme, we synthesized and characterized a series of nitro-masked psGSLs, including azide-, alkyne-, and fluorophore-functionalized derivatives. Enzymatic reduction induces a self-immolative 1,6-elimination and subsequent thio-Lossen rearrangement, releasing ITCs under physiological conditions. The liberated ITCs covalently modify peptides and proteins, showing predominant lysine reactivity in chemoproteomic analyses of the Staphylococcus aureus proteome, including functional sites of essential proteins. Fluorescent probes enabled visualization of enzyme-dependent protein labeling and demonstrated nitroreductase-triggered ITC release in vivo in Caenorhabditis elegans. Together, psGSLs establish a modular, bioresponsive prodrug and chemical biology platform for enzyme-controlled ITC delivery, expanding the scope of ITC-based covalent modification beyond natural myrosinase-dependent systems.

Enzyme engineering has evolved from random directed evolution to knowledge-guided rational design and is now entering an artificial intelligence (AI)-driven third wave. To capture AI’s transformative impact, we propose the investigate-design-execute-analyze (IDEA) framework, which illustrates how AI integrates across the entire enzyme engineering pipeline—from enzyme discovery and biocatalyst design to experimental validation and mechanistic analysis. This framework serves as a roadmap for leveraging advanced AI to reprogram enzyme engineering workflows, establishing a new paradigm for intelligent biocatalyst design.

Polyketides are prized for their structural complexity and therapeutic potential, yet the incorporation of amide bonds into their frameworks typically relies on linear, nonribosomal peptide synthetase (NRPS)-dependent assembly. The direct, convergent coupling of distinct polyketide chains via amide bond formation--an ideal strategy for combinatorial biosynthesis--has remained largely elusive. Here, we report the discovery of a novel family of arylamine N-acetyltransferases (NATs) from manumycin-type biosynthetic pathways that catalyze an unprecedented intermolecular amidative chain transfer/condensation between an acyl carrier protein (ACP)-tethered polyketide donor and a free polyketide acceptor. Biochemical, structural, and molecular dynamics studies reveal that the representative enzyme, ColC2, possesses a distinctive substrate-binding pocket that diverges from canonical arylamine NATs, conferring exceptional promiscuity toward diverse acyl donors and acceptors. We demonstrate the utility of this biocatalyst by coupling arylamines with either synthetic acyl-thioesters or polyketide synthase (PKS) machinery to generate a library of non-natural polyketide amides and manumycin derivatives. These findings establish a new paradigm for amide bond formation in polyketide biosynthesis and position arylamine NATs as powerful tools for the development of novel therapeutics through combinatorial synthesis.

We developed a deep learning pipeline for the rapid discovery of peptides with high affinity for polyethylene terephthalate. Fusing these peptides to a polyethylene terephthalate hydrolase substantially enhanced enzymatic degradation efficiency. This deep learning-guided strategy offers a powerful approach for engineering enhanced biocatalysts to mitigate plastic waste.

Nature, Published online: 16 April 2026; doi:10.1038/d41586-026-00509-9

Can you squeeze your graduate programme into a 40-hour working week? These 13 current and former PhD candidates reveal their top time-management tips.

Nature Chemistry, Published online: 16 April 2026; doi:10.1038/s41557-026-02122-9

The mechanism underlying the formation of ionophore polyethers—polyketide-derived natural products containing tetrahydrofuran and tetrahydropyran rings—has been elusive. Now structural and biochemical analyses reveal that a C26 linear precursor undergoes four successive cyclizations within the single active site of the heterodimeric polyether epoxide hydrolase MonBI·MonBII, in which MonBI promotes MonBII’s folded active conformation.

An integrated electroenzymatic platform synergizes engineered thiamine diphosphate (ThDP)-dependent radical biocatalysis with mediated electrochemical oxidation, achieving the highly enantioselective desymmetrization of dialdehydes to access silicon-stereogenic carboxylic acids. Harnessing electricity to access enzyme-bound radical intermediates unlocks a new-to-nature biocatalytic route to non-racemic silicon-stereogenic compounds.

ABSTRACT

Chiral silicon-stereogenic organosilanes are finding increasingly widespread applications in pharmaceutical science and biomedical materials. However, the enzymatic construction of silicon chiral centers remains underdeveloped. Here, we report the integration of thiamine diphosphate (ThDP)-dependent radical biocatalysis and mediated electrochemical oxidation to unlock non-natural enzymatic oxidative desymmetrization, enabling the highly enantioselective synthesis of silicon stereocenters. Using symmetric silane dialdehydes as substrates, variants of benzaldehyde lyase from Pseudomonas fluorescens (PfBAL) together with ferrocene methanol (FcMeOH) as a redox mediator facilitate selective oxidation. This method features a broad substrate scope, producing a range of enantioenriched silicon-containing carboxylic acids with excellent enantioselectivity (22 examples, up to >99.5% ee). Mechanistic investigations confirm substrate binding, explain the origin of enantioselectivity, and validate the mediated electron transfer pathway. This study expands the enzyme reactivity repertoire by merging electrochemical synthesis with biocatalysis, establishing an effective biocatalytic strategy for constructing silicon chirality.

Nitrogen fixation and nitrogen oxide reduction are central to sustainable ammonia production. This perspective compares enzymatic, molecular, and heterogeneous catalysts, highlighting mechanistic insights from nitrogenases to Li-mediated and electrocatalytic systems. Emphasis is placed on catalyst structure, microenvironment, and interfacial effects, outlining design principles for advancing nitrogen-cycle catalysis.

Communications Chemistry, Published online: 14 April 2026; doi:10.1038/s42004-026-01986-9

Fungal decarboxylases in the isopenicillin N synthase subfamily exhibit unique N- and C-terminal insertions, but the mechanistic roles of these elements remain largely elusive. Here, the authors report crystal structures of TraH in complex with various substrates, showing an N-terminal lid loop that undergoes substrate-dependent rearrangements, facilitating a distinct decarboxylation mechanism.

Biocatalysis against disease vectors: Engineered squalene-hopene cyclases catalyze a direct asymmetric Prins cyclohydration to selectively produce (1R)-cis-p-menthane-3,8-diol (PMD), a potent natural mosquito repellent. Strategic active site modifications enable a precisely positioned water molecule to drive carbocation hydration. Preparative-scale synthesis, access to all natural PMD isomers, as well as a cascade from citral, are also presented.

ABSTRACT

Vector-borne diseases pose a rising global health challenge, necessitating the development of safe and effective pest protection agents. Here, we report a highly selective biocatalytic direct Prins cyclohydration for the synthesis of (1R)-cis-p-menthane-3,8-diol (PMD), a natural insect repellent with high efficacy. By strategically engineering squalene-hopene cyclases (SHCs), we achieved >96% diastereomeric excess, surpassing previous synthetic methods. Structural and mechanistic analyses suggest direct Prins cyclohydration and a precisely positioned water molecule within the enzyme's active pocket adjacent to the final carbocation that drives hydration and catalytic efficiency. Fine-tuning the biocatalytic setup enabled preparative scale production, without losing much product selectivity. Moreover, we demonstrate access to the other naturally occurring PMD isomers from (R)- and (S)-citronellal, as well as a one-pot cascade starting from E/Z-citral. This study paves the way for highly selective access to stereodefined terpene-derived repellents and establishes engineered squalene-hopene cyclases as a tool for direct asymmetric Prins cyclohydration.

A concise three-step synthesis enables access to amino acid-derived adenosine vinylsulfonamide (AVS) probes under mild conditions. Ba(OH)₂-mediated coupling suppresses epimerization, affording stereochemically defined probes that covalently capture nonribosomal peptide synthetase (NRPS) thioesterification states. LC–MS/MS confirms functional engagement of an AVS probe with NRPS SfmC, supporting mechanistic and structural studies.

Adenosine vinylsulfonamide (AVS) probes provide a powerful means of stabilizing the thioesterification state in nonribosomal peptide synthetases (NRPSs) by mimicking aminoacyl-AMP intermediates. Existing synthetic strategies have enabled broad application of this probe class, yet they often rely on strongly basic conditions for constructing the key CC bond from α-amino aldehydes, substrates that are inherently prone to epimerization. These features limit practical access to AVS derivatives from nonproteinogenic amino acids, many of which are central to NRPS-mediated natural product biosynthesis. To address these constraints, we developed a concise three-step route beginning from N-Boc amino alcohols that proceeds under operationally simple and stereochemically controlled conditions. A preassembled adenosine phosphinyl sulfonamide serves as an effective coupling partner in a Ba(OH)₂-mediated Horner reaction performed near 0°C, enabling highly diastereoselective AVS formation with minimal epimerization under mild, open-air conditions. The method tolerates diverse amino acid-derived substrates, including electron-rich L-Tyr derivatives relevant to tetrahydroisoquinoline alkaloid biosynthesis. Functional evaluation by LC–MS/MS confirmed covalent capture of the NRPS SfmC by an L-Tyr-derived probe, demonstrating that AVS constructs prepared by this route retain full biochemical competence. This streamlined synthesis enhances reliable access to stereochemically well-defined AVS probes and supports structural and mechanistic studies across diverse NRPS systems.

Natural enzymes and artificial mimics face cost, instability, or complexity limitations in biomedicine. Nanozymes improve some aspects but lack clear structure–activity relationships. Single-atom catalysts bridge this gap, while single-atom nanozymes (SAzymes) with axial coordination further enhance enzyme-like activity by tuning electronic structures. This article reviews axially coordinated SAzymes from synthetic strategy, coordination design, to biomedical applications.

Natural enzymes and traditional artificial enzyme mimics are limited in biomedical applications by high costs, instability, or insufficient structural complexity. Nanozymes address some issues but lack sophistication and clear structure–activity relationships. Single-atom catalysts (SACs) bridge natural enzymes and nanozymes, while single-atom nanozymes (SAzymes) with tailored axial coordination further enhance enzyme-like activities by modulating electronic structures via axial ligands. Here we summarize advances in axially coordinated SAzymes for biomedicine: this review categorizes synthetic strategies (dominated by high-temperature pyrolysis, supplemented by solvothermal and supramolecular assembly methods); elaborates on axial coordination designs (nitrogen-group, chalcogen-containing, halogen-containing, and other ligands); and highlights applications in colorimetric biosensing, tumor therapy, and antimicrobial therapy. Finally, we outline challenges and perspectives on controllable synthesis, mechanism elucidation, biosafety to guide rational design and clinical translation of axially coordinated SAzymes.

Nature Synthesis, Published online: 13 April 2026; doi:10.1038/s44160-026-01053-0

A low-cost, modular self-driving laboratory platform (RoboChem-Flex) is designed to democratize autonomous chemical experimentation. This platform combines customizable hardware with Python-based control software to make advanced Bayesian optimization more accessible. Photochemical, biocatalytic and thermal processes are demonstrated, showcasing a broad range of potential applications in both fully closed-loop and human-in-the-loop approaches.