The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin.

Background: The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified.

Generation of Aurachin Derivatives by Whole-Cell Biotransformation and Evaluation of Their Antiprotozoal Properties.

The natural product aurachin D is a farnesylated quinolone alkaloid, which is known to possess activity against the causative agent of malaria, spp. In this study, we show that aurachin D inhibits other parasitic protozoa as well. While aurachin D had only a modest effect on , two other trypanosomatids, and , were killed at low micromolar and nanomolar concentrations, respectively, in an in vitro assay.

Biocatalytic C3-Indole Methylation-A Useful Tool for the Natural-Product-Inspired Stereoselective Synthesis of Pyrroloindoles.

Enantioselective synthesis of bioactive compounds bearing a pyrroloindole framework is often laborious. In contrast, there are several S-adenosyl methionine (SAM)-dependent methyl transferases known for stereo- and regioselective methylation at the C3 position of various indoles, directly leading to the formation of the desired pyrroloindole moiety. Herein, the SAM-dependent methyl transferase PsmD from Streptomyces griseofuscus, a key enzyme in the biosynthesis of physostigmine, is characterized in detail.

Metabolic specialization in itaconic acid production: a tale of two fungi.

Some of the oldest and most established industrial biotechnology processes involve the fungal production of organic acids. In these fungi, the transport of metabolites between cellular compartments, and their secretion, is a major factor. In this review we exemplify the importance of both mitochondrial and plasma membrane transporters in the case of itaconic acid production in two very different fungal systems, Aspergillus and Ustilago.

The NOP-1 peptide derived from the central regulator of ethylene signaling EIN2 delays floral senescence in cut flowers.

The plant hormone ethylene was identified as important triggering factor and primary regulator of flower senescence in many species. Consequently, application of chemical inhibitors of ethylene biosynthesis and action is used to extend the longevity of ethylene-sensitive flowers. Here, we show that the peptide NOP-1, a biological derived from the nuclear localization signal of ethylene regulator EIN2 tightly binds to the ethylene receptor of carnation plants - a model to study flower senescence.

Redesign of a New Manganese Peroxidase Highly Expressed in Pichia pastoris towards a Lignin-Degrading Versatile Peroxidase.

Manganese peroxidases, lignin peroxidases, and versatile peroxidases secreted by white rot fungi are supposed to play an essential role in lignin degradation. Thus, these enzymes have attracted significant attention as potential biocatalysts. Versatile peroxidases are the most interesting ones, since they comprise activities of manganese and lignin peroxidases.

Structure of the γ-ε complex of cyanobacterial F-ATPase reveals a suppression mechanism of the γ subunit on ATP hydrolysis in phototrophs.

F-ATPase forms the membrane-associated segment of FF-ATP synthase - the fundamental enzyme complex in cellular bioenergetics for ATP hydrolysis and synthesis. Here, we report a crystal structure of the central F subcomplex, consisting of the rotary shaft γ subunit and the inhibitory ε subunit, from the photosynthetic cyanobacterium BP-1, at 1.98 Å resolution.

Modelling phosphorus uptake in microalgae.

Phosphorus (P) is an essential non-renewable nutrient that frequently limits plant growth. It is the foundation of modern agriculture and, to a large extent, demand for P is met from phosphate rock deposits which are limited and becoming increasingly scarce. Adding an extra stroke to this already desolate picture is the fact that a high percentage of P, through agricultural runoff and waste, makes its way into rivers and oceans leading to eutrophication and collapse of ecosystems.

Recognition motif and mechanism of ripening inhibitory peptides in plant hormone receptor ETR1.

Synthetic peptides derived from ethylene-insensitive protein 2 (EIN2), a central regulator of ethylene signalling, were recently shown to delay fruit ripening by interrupting protein-protein interactions in the ethylene signalling pathway. Here, we show that the inhibitory peptide NOP-1 binds to the GAF domain of ETR1 - the prototype of the plant ethylene receptor family. Site-directed mutagenesis and computational studies reveal the peptide interaction site and a plausible molecular mechanism for the ripening inhibition.

Pyrazolidine-3,5-dione-based inhibitors of phosphoenolpyruvate carboxylase as a new class of potential C plant herbicides.

Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the C photosynthetic pathway of many of the world's worst weeds and a valuable target to develop C plant-selective herbicides. By virtual screening, analog synthesis, and in vitro validation, we identified pyrazolidine-3,5-diones as a new class of small molecules with inhibitory potential down to the submicromolar range against C PEPC and a selectivity factor of up to 16 over C PEPC. No other biological activity has yet been reported for the best compound, (3-bromophenyl)-4-(3-hydroxybenzylidene)-pyrazolidine-3,5-dione.

Probing the acetaldehyde-sensitivity of 2-deoxy-ribose-5-phosphate aldolase (DERA) leads to resistant variants.

The 2-deoxy-d-ribose-5-phosphate aldolase (DERA) is a synthetically attractive enzyme because of its ability to perform CC-couplings stereoselectively, the enzyme uses acetaldehyde as nucleophile and thus produces true aldols rather than ketols, and may add two acetaldehyde molecules onto one electrophile. However, DERA produces crotonaldehyde as side reaction from acetaldehyde which is then an irreversible inhibitor forming a covalent Michael-adduct within the active site in particular with cysteine 47 (Dick et al., 2016).

Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.

Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis.

Trading off stability against activity in extremophilic aldolases.

Understanding enzyme stability and activity in extremophilic organisms is of great biotechnological interest, but many questions are still unsolved. Using 2-deoxy-D-ribose-5-phosphate aldolase (DERA) as model enzyme, we have evaluated structural and functional characteristics of different orthologs from psychrophilic, mesophilic and hyperthermophilic organisms. We present the first crystal structures of psychrophilic DERAs, revealing a dimeric organization resembling their mesophilic but not their thermophilic counterparts.

Combinatorial optimization of synthetic operons for the microbial production of p-coumaryl alcohol with Escherichia coli.

Background: Microbes are extensively engineered to produce compounds of biotechnological or pharmaceutical interest. However, functional integration of synthetic pathways into the respective host cell metabolism and optimization of heterologous gene expression for achieving high product titers is still a challenging task. In this manuscript, we describe the optimization of a tetracistronic operon for the microbial production of the plant-derived phenylpropanoid p-coumaryl alcohol in Escherichia coli.