Chemical synthesis in competition with global genome mining and heterologous expression for the preparation of dimeric tryptophan-derived 2,5-dioxopiperazines

Covering: up to the end of 2021 Within the 2,5-dioxopiperazines-containing natural products, those generated from tryptophan allow further structural diversification due to the rich chemical reactivity of the indole heterocycle. The great variety of natural products, ranging from simple dimeric bispyrrolidinoindoline dioxopiperazines and tryptophan-derived dioxopiperazine/pyrrolidinoindoline dioxopiperazine analogs to complex polycyclic downstream metabolites containing transannular connections between the subunits, will be covered. These natural products are constructed by Nature using hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) assembly lines. Mining of microbial genome sequences has more recently allowed the study of the metabolic routes and the discovery of their hidden biosynthetic potential. The competition (ideally, also the combined efforts) between their isolation from the cultures of the producing microorganisms after global genome mining and heterologous expression and the synthetic campaigns, has more recently allowed the successful generation and structural confirmation of these natural products. Their biological activities as well as their proposed biogenetic routes and computational studies on biogenesis will also be covered.

Automated summary

This article covers the research progress of 2,5-dioxopiperazine-containing natural products up to the end of 2021, with a focus on those derived from tryptophan. These products exhibit diverse structures and are constructed by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) assembly lines. Recent studies have successfully synthesized these natural products through the mining of microbial genome sequences and competition between heterologous expression and synthetic campaigns, allowing for the investigation of their biological activities and biosynthetic pathways.