Hajo Kries
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View article: Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases
Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases Open
Nonribosomal peptide synthetases (NRPSs) are sophisticated molecular machines that biosynthesize peptide drugs. In attempts to generate new bioactive compounds, some parts of NRPSs have been successfully manipulated, but especially the inf…
View article: Analysing Megasynthetase Mutants at High Throughput Using Droplet Microfluidics**
Analysing Megasynthetase Mutants at High Throughput Using Droplet Microfluidics** Open
Nonribosomal peptide synthetases (NRPSs) are giant enzymatic assembly lines that deliver many pharmaceutically valuable natural products, including antibiotics. As the search for new antibiotics motivates attempts to redesign nonribosomal …
View article: Novel Biocatalysts from Specialized Metabolism
Novel Biocatalysts from Specialized Metabolism Open
Enzymes are increasingly recognized as valuable (bio)catalysts that complement existing synthetic methods. However, the range of biotransformations used in the laboratory is limited. Here we give an overview on the biosynthesis‐inspired di…
View article: Directed Evolution of Piperazic Acid Incorporation by a Nonribosomal Peptide Synthetase**
Directed Evolution of Piperazic Acid Incorporation by a Nonribosomal Peptide Synthetase** Open
Engineering of biosynthetic enzymes is increasingly employed to synthesize structural analogues of antibiotics. Of special interest are nonribosomal peptide synthetases (NRPSs) responsible for the production of important antimicrobial pept…
View article: Directed evolution of piperazic acid incorporation by a nonribosomal peptide synthetase
Directed evolution of piperazic acid incorporation by a nonribosomal peptide synthetase Open
Engineering of biosynthetic enzymes is increasingly employed to synthesize structural analogues of antibiotics. Of special interest are non-ribosomal peptide synthetases (NRPSs) responsible for production of important antimicrobial peptide…
View article: Screening megasynthetase mutants at high throughput using droplet microfluidics
Screening megasynthetase mutants at high throughput using droplet microfluidics Open
Nonribosomal peptide synthetases (NRPSs) are giant enzymatic assembly lines that deliver many pharmaceutically valuable natural products, including antibiotics. As the search for new antibiotics motivates attempts to redesign nonribosomal …
View article: Biosynthetic incorporation of fluorinated amino acids into the nonribosomal peptide gramicidin S
Biosynthetic incorporation of fluorinated amino acids into the nonribosomal peptide gramicidin S Open
Since fluorinated compounds are vital in medicinal chemistry, incorporating fluorine into natural products is attracting interest. We enable incorporation of 4-fluoro-Phe into the nonribosomal peptide gramicidin S with a surgical mutation.
View article: Defining a Nonribosomal Specificity Code for Design
Defining a Nonribosomal Specificity Code for Design Open
Nonribosomal peptide synthetases (NRPSs) assemble bioactive peptides from an enormous repertoire of building blocks. How binding pocket residues of the nonribosomal adenylation domain, the so-called specificity code, determine which buildi…
View article: Proof-Reading Thioesterase Boosts Activity of Engineered Nonribosomal Peptide Synthetase
Proof-Reading Thioesterase Boosts Activity of Engineered Nonribosomal Peptide Synthetase Open
Nonribosomal peptide synthetases (NRPSs) are a vast source of valuable natural products, and re-engineering them is an attractive path toward structurally diversified active compounds. NRPS engineering often requires heterologous expressio…
View article: Mikrobielle Antibiotikafabriken verstehen und verbessern
Mikrobielle Antibiotikafabriken verstehen und verbessern Open
Repurposing the enzymes in microbial metabolism such as nonribosomal peptide synthetases (NRPSs) is explored as a route towards better antibiotics. NRPSs are gigantic enzymatic assembly lines that form highly modified peptides from diverse…
View article: Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in<i>Salpingoeca rosetta</i>
Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in<i>Salpingoeca rosetta</i> Open
The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), whi…
View article: Macrophage-targeting oligopeptides from <i>Mortierella alpina</i>
Macrophage-targeting oligopeptides from <i>Mortierella alpina</i> Open
Specificity profiling of a nonribosomal peptide synthetase of an early diverging fungus revealed high substrate flexibility. Feeding studies with click-functionalised amino acids enabled the production of fluorescent peptides targeting mac…
View article: An Engineered Nonribosomal Peptide Synthetase Shows Opposite Amino Acid Loading and Condensation Specificity
An Engineered Nonribosomal Peptide Synthetase Shows Opposite Amino Acid Loading and Condensation Specificity Open
Engineering of nonribosomal peptide synthetases (NRPS) has faced numerous obstacles despite being an attractive path towards novel bioactive molecules. Specificity filters in the nonribosomal peptide assembly line determine engineering su…
View article: An Engineered Nonribosomal Peptide Synthetase Shows Opposite Amino Acid Loading and Condensation Specificity
An Engineered Nonribosomal Peptide Synthetase Shows Opposite Amino Acid Loading and Condensation Specificity Open
Engineering of nonribosomal peptide synthetases (NRPS) has faced numerous obstacles despite being an attractive path towards novel bioactive molecules. Specificity filters in the nonribosomal peptide assembly line determine engineering suc…
View article: Bacterial-Like Nonribosomal Peptide Synthetases Produce Cyclopeptides in the Zygomycetous Fungus Mortierella alpina
Bacterial-Like Nonribosomal Peptide Synthetases Produce Cyclopeptides in the Zygomycetous Fungus Mortierella alpina Open
Fungal natural compounds are industrially produced, with application in antibiotic treatment, cancer medications, and crop plant protection. Traditionally, higher fungi have been intensively investigated concerning their metabolic potentia…
View article: Bacterial-like nonribosomal peptide synthetases produce cyclopeptides in the zygomycetous fungus<i>Mortierella alpina</i>
Bacterial-like nonribosomal peptide synthetases produce cyclopeptides in the zygomycetous fungus<i>Mortierella alpina</i> Open
Fungi are traditionally considered as reservoir of biologically active natural products. However, an active secondary metabolism has long not been attributed to early diverging fungi such as Mortierella spec . Here, we report on the biosyn…
View article: Engineering DNA templated nonribosomal peptide synthesis
Engineering DNA templated nonribosomal peptide synthesis Open
Nanocontainers or macromolecular scaffolds for artificial biocatalytic cascades facilitate sequential enzyme reactions but diffusive escape of intermediates limits rate enhancement. Nonribosomal peptide synthetases (NRPS) naturally form gi…
View article: Sulfonium Acids Loaded onto an Unusual Thiotemplate Assembly Line Construct the Cyclopropanol Warhead of a <i>Burkholderia</i> Virulence Factor
Sulfonium Acids Loaded onto an Unusual Thiotemplate Assembly Line Construct the Cyclopropanol Warhead of a <i>Burkholderia</i> Virulence Factor Open
Pathogenic bacteria of the Burkholderia pseudomallei group cause severe infectious diseases such as glanders and melioidosis. Malleicyprols were identified as important bacterial virulence factors, yet the biosynthetic origin of their cycl…
View article: Sulfonium Acids Loaded onto an Unusual Thiotemplate Assembly Line Construct the Cyclopropanol Warhead of a <i>Burkholderia</i> Virulence Factor
Sulfonium Acids Loaded onto an Unusual Thiotemplate Assembly Line Construct the Cyclopropanol Warhead of a <i>Burkholderia</i> Virulence Factor Open
Pathogenic bacteria of the Burkholderia pseudomallei group cause severe infectious diseases such as glanders and melioidosis. Malleicyprols were identified as important bacterial virulence factors, yet the biosynthetic origin of their cycl…
View article: Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme
Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme Open
Temperature influences the reaction kinetics and evolvability of all enzymes. To understand how evolution shapes the thermodynamic drivers of catalysis, we optimized the modest activity of a computationally designed enzyme for an elementar…
View article: Frontispiece: Biocatalytic Strategies towards [4+2] Cycloadditions
Frontispiece: Biocatalytic Strategies towards [4+2] Cycloadditions Open
Biocatalysis and synthetic organic chemistry play by the same physicochemical rules, but their strong suits are fundamentally different. A case in point are cycloaddition reactions: their wide use in synthetic organic chemistry contrasts w…
View article: Structure elucidation of the syringafactin lipopeptides provides insight in the evolution of nonribosomal peptide synthetases
Structure elucidation of the syringafactin lipopeptides provides insight in the evolution of nonribosomal peptide synthetases Open
A snapshot of evolution in flagrante shows that recombination within and between biosynthetic genes leads to diversification of nonribosomal peptides.
View article: HAMA: a multiplexed LC-MS/MS assay for specificity profiling of adenylate-forming enzymes
HAMA: a multiplexed LC-MS/MS assay for specificity profiling of adenylate-forming enzymes Open
Adenylation enzymes are engineering targets in ribosomal and nonribosomal peptide synthesis. Through multiplexed LC-MS/MS measurement of hydroxamates, the HAMA assay records specificity profiles of these enzymes in a snap.
View article: CCDC 1560105: Experimental Crystal Structure Determination
CCDC 1560105: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 1560104: Experimental Crystal Structure Determination
CCDC 1560104: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Biocatalysts from alkaloid producing plants
Biocatalysts from alkaloid producing plants Open
Metabolic pathways leading to benzylisoquinoline and monoterpene indole alkaloids in plants are revealing remarkable new reactions. Understanding of the enzymes involved in alkaloid biosynthesis provides access to a variety of applications…
View article: Identification and Characterization of the Iridoid Synthase Involved in Oleuropein Biosynthesis in Olive (Olea europaea) Fruits
Identification and Characterization of the Iridoid Synthase Involved in Oleuropein Biosynthesis in Olive (Olea europaea) Fruits Open
The secoiridoids are the main class of specialized metabolites present in olive (Olea europaea L.) fruit. In particular, the secoiridoid oleuropein strongly influences olive oil quality because of its bitterness, which is a desirable trait…