Biocatalytic Tetrapeptide Macrocyclization by Cryptic Penicillin-binding Protein-type Thioesterases.

Cyclic tetrapeptides (CTPs) are a diverse class of natural products with a broad range of biological activities. However, they are extremely challenging to synthesize due to the ring strain associated with their small ring size. While chemical methods have been developed to access CTPs, they generally require the presence of certain amino acids, limiting their substrate scopes.

Activity and Biocatalytic Potential of an Indolylamide Generating Thioesterase.

The chemical synthesis of -acyl indoles is hindered by the poor nucleophilicity of indolic nitrogen, necessitating the use of strongly basic reaction conditions that encumber elaboration of highly functionalized scaffolds. Herein, we describe the total chemoenzymatic synthesis of the bulbiferamide natural products by the biochemical activity reconstitution of a nonribosomal peptide synthetase assembly line-derived (NRPS-derived) thioesterase that neatly installs the macrocyclizing indolylamide. The enzyme represents a starting point for biocatalytic access to macrocyclic indolylamide peptides and natural products.

Biocatalytic cyclization of small macrolactams by a penicillin-binding protein-type thioesterase.

Macrocyclic peptides represent promising scaffolds for chemical tools and potential therapeutics. Synthetic methods for peptide macrocyclization are often hampered by C-terminal epimerization and oligomerization, leading to difficult scalability. While chemical strategies to circumvent this issue exist, they often require specific amino acids to be present in the peptide sequence.

Synthetic Natural Product Inspired Cyclic Peptides.

Natural products are a bountiful source of bioactive molecules. Unfortunately, discovery of novel bioactive natural products is challenging due to cryptic biosynthetic gene clusters, low titers, and arduous purifications. Herein, we describe SNaPP (ynthetic tural roduct Inspired Cyclic eptides), a method for identifying NP-inspired bioactive peptides.

Electroanalysis and Spectroelectrochemistry of Nonaromatic Explosives in Acetonitrile Containing Dissolved Oxygen.

In search of a rapid, low-cost, and solution-phase detection technique for explosives, the (spectro-)electrochemistry of compounds from two major nonaromatic classes, namely nitramines (RDX and HMX) and nitrate esters (pentaerythritol tetranitrate (PETN) and the plastic explosive composite Semtex 1A) in acetonitrile (AN) is reported. In electrochemical screening, 5 μg of explosive material was detectable in 10 s by multicomponent cyclic voltammetric (CV) analysis on unmodified glassy carbon under ubiquitous environmental influences (i.e.