Characterization of a Dual Function Peptide Cyclase in Graspetide Biosynthesis.

Graspetides are a diverse family of ribosomally synthesized and post-translationally modified peptides with unique macrocyclic structures formed by ATP-grasp enzymes. Group 11 graspetides, including prunipeptin, feature both macrolactone and macrolactam cross-links. Despite the known involvement of a single ATP-grasp cyclase in the dual macrocyclizations of groups 5, 7, and 11 graspetides, detailed mechanistic insights into these enzymes remain limited.

Biosynthesis of Lyngbyastatins 1 and 3, Cytotoxic Depsipeptides from an sp. Marine Cyanobacterium.

Lyngbyastatins (Lbns) 1 () and 3 () belong to a group of cyclic depsipeptides that inhibit cancer cell proliferation. These compounds have been isolated from different marine cyanobacterial collections, while further development of these compounds relies on their lengthy total synthesis. Biosynthetic studies of these compounds can provide viable strategies to access these compounds and develop new analogs.

Metabolite profiling reveals organ-specific flavone accumulation in and identifies a scutellarin isomer isoscutellarein 8--β-glucuronopyranoside.

is a genus of plants containing multiple species with well-documented medicinal effects. and are among the best-studied species, and previous works have established flavones to be the primary source of their bioactivity. Recent genomic and biochemical studies with and have advanced our understanding of flavone biosynthesis in .

Biocatalytic synthesis of peptidic natural products and related analogues.

Peptidic natural products (PNPs) represent a rich source of lead compounds for the discovery and development of therapeutic agents for the treatment of a variety of diseases. However, the chemical synthesis of PNPs with diverse modifications for drug research is often faced with significant challenges, including the unavailability of constituent nonproteinogenic amino acids, inefficient cyclization protocols, and poor compatibility with other functional groups. Advances in the understanding of PNP biosynthesis and biocatalysis provide a promising, sustainable alternative for the synthesis of these compounds and their analogues.

Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

Mycosporine-like amino acids (MAAs) are a family of natural products that are produced by a variety of organisms for protection from ultraviolet damage. In this work, we combined different bioinformatic approaches to assess the distribution of the MAA biosynthesis and identified a putative gene cluster from NIES-25 that encodes a short-chain dehydrogenase/reductase and a nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase (MysH) as potential new biosynthetic enzymes. Heterologous expression of refactored gene clusters in produced two known biosynthetic intermediates, 4-deoxygadusol and mycosporine-glycine, and three disubstituted MAA analogues, porphyra-334, shinorine, and mycosporine-glycine-alanine.

Aldoximes are precursors of auxins in Arabidopsis and maize.

Two natural auxins, phenylacetic acid (PAA) and indole-3-acetic acid (IAA), play crucial roles in plant growth and development. One route of IAA biosynthesis uses the glucosinolate intermediate indole-3-acetaldoxime (IAOx) as a precursor, which is thought to occur only in glucosinolate-producing plants in Brassicales. A recent study showed that overproducing phenylacetaldoxime (PAOx) in Arabidopsis increases PAA production.

Recent advances in the biosynthesis of RiPPs from multicore-containing precursor peptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) compose a large structurally and functionally diverse family of natural products. The biosynthesis system of RiPPs typically involves a precursor peptide comprising of a leader and core motif and nearby processing enzymes that recognize the leader and act on the core for producing modified peptides. Interest in RiPPs has increased substantially in recent years as improvements in genome mining techniques have dramatically improved access to these peptides and biochemical and engineering studies have supported their applications.