Formation of Bridged Disulfide in Epidithiodioxopiperazines

• Published in: Chembiochem : a European journal of chemical biology Vol. 25; no. 6; pp. e202300770 - n/a
• Main Authors: Fan, Jie, Wei, Peng‐Lin, Yin, Wen‐Bing
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 15.03.2024
• Subjects: Biosynthesis; catalytic mechanism; Chemical synthesis; Complexity; disulfide; Disulfide bonds; Disulfides - chemistry; epidithiodioxopiperazines; Flavin; flavin-containing oxygenase; Industrial applications; Piperazines - chemistry; flavin-containing oxygenase; catalytic mechanism; epidithiodioxopiperazines; disulfide; biosynthesis
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202300770

Epidithiodioxopiperazine (ETP) alkaloids, featuring a 2,5‐diketopiperazine core and transannular disulfide bridge, exhibit a broad spectrum of biological activities. However, the structural complexity has prevented efficient chemical synthesis and further clinical research. In the past few decades, many achievements have been made in the biosynthesis of ETPs. Here, we discuss the biosynthetic progress and summarize them as two comprehensible metabolic principles for better understanding the complex pathways of α, α′‐ and α, β′‐disulfide bridged ETPs. Specifically, we systematically outline the catalytic machineries to install α, α′‐ and α, β′‐disulfide by flavin‐containing oxygenases. This concept would contribute to the medical and industrial applications of ETPs. Epidithiodioxopiperazines (ETPs) alkaloids possess complex structures and exhibit a broad spectrum of biological activities. In this concept, we summarize the biosynthesis of α, α′‐ and α, β′‐disulfide bridged ETPs and outline the catalytic machineries for the transannular disulfide construction. This will facilitate the medical and industrial applications of ETPs.