In plant cells, plastids form elongated extensions called stromules, the regulation and purposes of which remain unclear. Here, we quantitatively explore how different stromule structures serve to enhance the ability of a plastid to interact with other organelles: increasing the effective space for interaction and biomolecular exchange between organelles. Interestingly, electron microscopy and confocal imaging showed that the cytoplasm in Arabidopsis thaliana and Nicotiana benthamiana epidermal cells is extremely thin (around 100 nm in regions without organelles), meaning that inter-organelle interactions effectively take place in 2D. We combine these imaging modalities with mathematical modeling and new in planta experiments to demonstrate how different stromule varieties (single or multiple, linear or branching) could be employed to optimize different aspects of inter-organelle interaction capacity in this 2D space. We found that stromule formation and branching provide a proportionally higher benefit to interaction capacity in 2D than in 3D. Additionally, this benefit depends on optimal plastid spacing. We hypothesize that cells can promote the formation of different stromule architectures in the quasi-2D cytoplasm to optimize their interaction interface to meet specific requirements. These results provide new insight into the mechanisms underlying the transition from low to high stromule numbers, the consequences for interaction with smaller organelles, how plastid access and plastid to nucleus signaling are balanced and the impact of plastid density on organelle interaction.

The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.

Fungal unspecific peroxygenases (UPOs) have gained substantial attention for their versatile oxyfunctionalization chemistry paired with impressive catalytic capabilities. A major drawback, however, remains their sensitivity towards their co‐substrate hydrogen peroxide, necessitating the use of smart in situ hydrogen peroxide generation methods to enable efficient catalysis setups. Herein, we introduce flavin‐containing protein photosensitizers as a new general tool for light‐controlled in situ hydrogen peroxide production. By genetically fusing flavin binding fluorescent proteins and UPOs, we have created two virtually self‐sufficient photo‐enzymes (PhotUPO). Subsequent testing of a versatile substrate panel with the two divergent PhotUPOs revealed two stereoselective conversions. The catalytic performance of the fusion protein was optimized through enzyme and substrate loading variation, enabling up to 24300 turnover numbers (TONs) for the sulfoxidation of methyl phenyl sulfide. The PhotUPO concept was upscaled to a 100 mg substrate preparative scale, enabling the extraction of enantiomerically pure alcohol products.Graphical Abstract Unspecific peroxygenases (UPOs) have recently gained attraction as versatile oxyfunctionalization catalysts. One shortcoming, however, is their susceptibility towards the co-substrate hydrogen peroxide. As a solution, the concept of light-dependent UPO biocatalysis with genetically encoded flavin-containing photosensitizer proteins for in situ hydrogen peroxide production is introduced.

Research data management (RDM) is needed to assist experimental advances and data collection in the chemical sciences. Many funders require RDM because experiments are often paid for by taxpayers and the resulting data should be deposited sustainably for posterity. However, paper notebooks are still common in laboratories and research data is often stored in proprietary and/or dead-end file formats without experimental context. Data must mature beyond a mere supplement to a research paper. Electronic lab note-books (ELN) and laboratory information managementsystems (LIMS) allow researchers to manage data better and they simplify research and publication. Thus, an agreement is needed on minimum information standards for data handling to support structured approaches to data reporting. As digitalization becomes part of curricular teaching, future generations of digital native chemists will embrace RDM and ELN as an organic part of their research.

In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants.

Plant cell walls are sophisticated carbohydrate-rich structures representing the immediate contact surface with the extracellular environment, often serving as the first barrier against biotic and abiotic stresses. Notably, a variety of perturbations in plant cell walls result in upregulated jasmonate (JA) production, a phytohormone with essential roles in defense and growth responses. Hence, cell wall-derived signals can initiate intracellular JA-mediated responses and the elucidation of the underlying signaling pathways could provide novel insights into cell wall maintenance and remodeling, as well as advance our understanding on how is JA biosynthesis initiated. This Mini Review will describe current knowledge about cell wall-derived damage signals and their effects on JA biosynthesis, as well as provide future perspectives.

The functionalization of C−H bonds with non‐precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof‐of‐concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C−H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines.

For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.

An important development in the field of macrocyclization strategies towards molecular cages is described. The approach comprises the utilization of a double Ugi four‐component macrocyclization for the assembly of macromulticycles with up to four different tethers, that is, hybrid cages. The innovation of this method rests on setting up the macromulticycle connectivities not through the tethers but through the bridgeheads, which in this case involve N‐substituted amino acids. Both dilution and metal‐template‐driven macrocyclization conditions were implemented with success, enabling the one‐pot formation of cryptands and cages including steroidal, polyether, heterocyclic, peptidic, and aryl tethers. This method demonstrates substantial complexity‐generating character and is suitable for applications in molecular recognition and catalysis.

In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.