A Review of Plant-Derived Diterpenoid Biosynthesis: From Structural Scaffold Diversity and Lineage-Associated Distribution to Enzyme Mining and Discovery Strategies
TL;DR
It is proposed that scaffold enrichment in specific evolutionary lineages, when integrated with enzyme family expansion and functional divergence, may provide a complementary framework for prioritizing candidate tailoring enzymes.
Abstract
Plant diterpenoids are a diverse class of natural products with important ecological roles and wide applications in the pharmaceutical, agricultural, food additive, and chemical industries. Biosynthesis represents a primary strategy for accessing these valuable compounds. However, the identification of downstream tailoring enzymes (hereafter referred to as tailoring enzymes) involved in diterpenoid biosynthetic pathways remains a major bottleneck, particularly in non-model plant species with limited genomic resources. This review summarizes current strategies for discovering plant diterpenoid biosynthetic pathways and recent advances in elucidating their metabolic routes. We further highlight the lineage-biased distribution of diterpene scaffolds across plant taxa. We propose that scaffold enrichment in specific evolutionary lineages, when integrated with enzyme family expansion and functional divergence, may provide a complementary framework for prioritizing candidate tailoring enzymes. Importantly, scaffold enrichment alone cannot establish enzyme function or evolutionary causality; rather, it provides a complementary layer of evidence that can guide future experimental investigation. Future perspectives include predictive substrate–enzyme mapping, computational and generative design of cytochrome P450 enzymes, and the integration of enzyme discovery, structural modeling, and heterologous chassis engineering.