Biosynthesis of indole diterpenes: a reconstitution approach in a heterologous host

Covering: 2013 to 2022 In this review, we provide an overview elucidating the biosynthetic pathway and heterologous production of fungal indole diterpenes (IDTs). Based on the studies of six IDT biosynthesis, we extracted nature's strategy: (1) two-stage synthesis for the core scaffold and platform intermediates, and (2) late-stage modifications for installing an additional cyclic system on the indole ring. Herein, we describe reconstitution studies applying this strategy to the synthesis of highly elaborated IDTs. We also discuss its potential for future biosynthetic engineering.

Automated summary

In this review, the biosynthetic pathway and heterologous production of fungal indole diterpenes (IDTs) are discussed. It is found that nature's strategy involves a two-stage synthesis for the core scaffold and platform intermediates, and late-stage modifications for installing an additional cyclic system on the indole ring. The potential of applying this strategy in the synthesis of highly elaborated IDTs and future biosynthetic engineering is also addressed.