Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• : Cage designs often face unstructured criticism for being either too flexible [146] or too rigid [25] to mimic enzymes. This is not the place for a detailed discussion on the nuances of these vague terms in enzymology [392][393][394], but we hope the following is persuasive. In considering the relative

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• . Their privileged structures have led organic and bioorganic chemists to develop methods to construct them. Our fundamental knowledge in enzymology is continually expanded by enzymes involved in natural products biosynthesis, as their production requires evolved enzymes to perform chemical reactions

• distinct from those seen in primary metabolism. Natural products have inspired generations of scientists and continue to do so today. This thematic issue highlights young investigators in natural products chemistry, biosynthesis, and enzymology. As early-career researchers ourselves, we are honored to

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• protect bacteria from exposure to NNG. Keywords: enzymology; natural products; nitramine; N–N bond; Introduction Degradation of nitramines (R–N(R′)NO2; R′ = H or alkyl) has been well studied in the context of the environmental degradation of explosive cyclic nitramines [1][2]. The cyclic nitramines

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• aforementioned NPRS macrocycles, the synthesis of macrocylic polyketides and PKS/NRPS hybrids is more challenging due to the absence of a streamlined preparation strategy such as solid-phase peptide synthesis (SPPS). In enzymology studies, it was common to hydrolyze the cyclic natural products in order to obtain

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• Japan Foundation for Applied Enzymology and the Research Foundation for Pharmaceutical Sciences to F.I. and a Grant-in Aid for Scientific Research on Innovative Areas (17H06401 to H.K.) and for Transformative Research Area (A) (23H04882 to H.K.) from the Ministry of Education Culture, Sports, Science

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• general discussion of various aspects of these equilibrium measurements as well as STRENDA (Standards for Reporting Enzymology Data) recommendations regarding the measurements and the reporting of results. Keywords: enzyme-catalyzed reactions; equilibrium constant; standards; thermodynamics; Perspective

• 1. Introduction and motivation for recommendations The aim of the STRENDA (Standards for Reporting Enzymology Data) Commission [1] is to establish standards for reporting the results of measurements related to enzymology with the aim to improve the quality and the findability, accessibility

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• , requiring a sophisticated enzymology [4]. Recent developments show us that there is still much more to discover, e.g., altemicidin was shown to be enzymatically constructed from NAD+ and SAM that usually serve as enzyme cosubstrates in redox transformations and methylations but are rarely used to construct

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• –10 mM. Interestingly, while compound 1bα showed a dose-dependent inhibitory effect in this experiment, compound 3a did not (Table 2). Although the crude system that we used in the enzymology experiments precludes precise kinetic characterization of the studied inhibitors on the target enzyme, GlfT2

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• . However, in the broader context of bioactive chemistry, it becomes indivisible from the related domains of chemical biology (directed towards mechanistic insight rather that direct drug discovery), enzymology, pharmacology, and toxicology in addition to the development of insecticides or herbicides

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• within the PTases, as the natural metalloprotein has been utilized as a model to create an artificial metalloprotein [36][37]. The increasing knowledge obtained from the X-ray structural studies of the PTases will contribute to the development of the enzymology and the chemoenzymatic syntheses of

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• to build synthetic metabolism. Here I discuss the current challenges and limitations in synthetic metabolic engineering and elucidate how modern day enzymology can help to build a synthetic metabolism of the future. Keywords: enzymes; in vitro biochemistry; metabolic engineering; synthetic biology

• bottom-up might represent a valuable alternative strategy [6]. Linking enzymology and synthetic biology In summary, synthetic biology can develop its full potential, if it becomes able to harness the diversity of the millions of different enzyme variants and homologs that naturally exist. While such

• information is collected and made available by many enzymology and biochemistry laboratories worldwide in a community effort, it is not provided in an optimal way so that it can be used for the synthetic metabolism community. How could this apparent gap be bridged? First, it will be necessary to collect

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• quantitative analysis, fulfilling the major goal of their work [1][2]. Estimating the binding affinity for the substrate as KS was an added bonus. These were profound discoveries that laid the foundation for enzymology throughout the 20th century. The Michaelis–Menten equation was originally derived assuming

• parameters takes on new significance in the current era of enzymology where the emphasis is on relating the parameters to individual rate constants and to structural and chemical transitions for each reaction in the pathway. While kcat/Km can be directly interpreted in terms of enzyme specificity, it also

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• and Economics, H-1521 Budapest, Hungary 1st Department of Medicine, University of Szeged, Korányi fasor 8–10, H-6720 Szeged, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• , Hungary Research Centre for Natural Sciences, Institute of Enzymology, Hungarian Academy of Sciences, 1117 Budapest, Hungary MTA-ELTE Protein Modelling Research Group, Hungarian Academy of Sciences, Eötvös L. University, 1117 Budapest, Hungary Department of Biopharmacy, Faculty of Pharmacy, University of

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• in a genome-led approach to the uncovering of novel enzymology in the biosynthetic pathways to antibiotic natural products [23][24][25][26]. Here, we have used in-house whole-genome sequencing to characterise the closely-related gene clusters to the sulfated antifungal linear polyenes clethramycin

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• all classes and they often contribute significantly to their biological activity. Progress in recent years has led to a much better understanding of their biosynthesis. In this context, plenty of novel enzymology has been discovered, suggesting that these pathways are an attractive target for future

• studies. Keywords: biosynthesis; chemoenzymatic synthesis; enzymology; heterocycles; polyketides; Introduction Heterocycles Heterocycles are important structural elements, which are present in natural products from all classes and also in many biologically active synthetic compounds. They often

• cyclisation modes triggers the interest on the responsible enzymes. Due to the relevance of heterocycles, understanding the enzymology of heterocycle formation is also an important milestone on the way to using the enzymes as chemoenzymatic tools in natural product synthesis and medicinal chemistry [6][7

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• pairs, respectively. The availability of this new concept for the assembly of large DNA constructs from multiple inexpensive single-stranded oligonucleotides, together with the chemistry and enzymology needed to convert unnatural assemblies into entirely natural assemblies, creates the need for a