In this article, we will delve into the fascinating world of Paxilline and its impact on today's society. From its origins to its relevance today, Paxilline has been the subject of study and interest by academics, researchers and enthusiasts from different disciplines. This article aims to analyze the influence of Paxilline on various aspects of our daily lives, as well as its role in shaping our culture, values and beliefs. Through an interdisciplinary approach, we will explore the many facets of Paxilline, shedding light on its importance and meaning in the contemporary context.
Paxilline was found to significantly extend the lifespan, healthspan, and mobility of aged C. elegans worms, but had no such effect on young worms. Paxilline was not found to induce seizures when injected intracerebroventricularly in mice but paradoxically had anticonvulsant activity against picrotoxin and pentylenetetrazol seizures in mice. It has also been used in mice to induce autism-like behaviors through inhibition of the BK channel.
Biosynthesis
Paxiline biosynthesis starts with the synthesis of geranylgeranyl pyrophosphate via the terpenoid pathway and indole-3-glycerol phosphate, which is an intermediate in the tryptophan biosynthesis pathway. By expressing six genes known to be necessary for Paxilline synthesis in Aspergillus oryzae, the further steps in the biosynthesis were identified; two epoxidations and two cyclizations yield paspaline, then two oxidation reactions and a demethylation complete the synthesis. This biosynthesis is notable for its unusual stereospecific polycyclization mechanism that has not been replicated in a chemical synthesis, though other mechanisms have been devised for total synthesis of Paxilline. Paxilline has also been found to be mono- or di-prenylated with DMAPP by an atypical prenyltransferase enzyme.