Changfeng Guo

Terpenoids, which are essential pharmaceutical compounds, encounter significant production challenges due to their low yields in native plants and associated ecological concerns. This review summarizes recent advances in metabolic engineering strategies applied across three complementary platforms: native medicinal plants, microbial systems, and heterologous plant hosts. We present how the “Genomic Insights to Biotechnological Applications” paradigm, supported by multi-omics technologies such as genomics, transcriptomics, metabolomics, and related disciplines, contributes to advancing research in this field. These technologies enable the systematic identification of key biosynthetic genes and regulatory networks. CRISPR-based tools, enzyme engineering, and subcellular targeting are presented as pivotal transformative strategies in advancing metabolic engineering approaches. Strategic co-expression and optimization approaches have achieved substantial improvements in product yields, as demonstrated by a 25-fold increase in paclitaxel production and a 38% enhancement in artemisinin yield. Persistent challenges, such as metabolic flux balancing, cytotoxicity, and scale-up economics, are discussed in conjunction with emerging solutions, including machine learning and photoautotrophic chassis systems. We conclude by proposing a strategic roadmap for industrial translation that highlights the essential integration of systems biology and synthetic biology approaches to accelerate the transition of terpenoid biomanufacturing from discovery to commercial-scale application.

Terpenoids, vital pharmaceutical compounds, face production challenges due to low yields in native plants and ecological concerns. This review synthesizes recent advances in metabolic engineering strategies implemented across three complementary platforms: native medicinal plants, microbial systems, and heterologous plant hosts. We elucidate how the "Genomic Insights to Biotechnological Applications" paradigm, empowered by multi-omics technologies such as genomics, transcriptomics, metabolomics, etc., drives research advancements. These technologies facilitate the identification of key biosynthetic genes and regulatory networks. CRISPR-based tools, enzyme engineering, and subcellular targeting are highlighted as transformative strategies. Significant yield improvements have been demonstrated, with artemisinin and paclitaxel precursors showing considerable increases in production through strategic co-expression and optimization techniques. Persistent challenges such as metabolic flux balancing, cytotoxicity, and scale-up economics are discussed alongside emerging solutions including machine learning and photoautotrophic chassis. We conclude by outlining a roadmap for industrial translation that emphasizes the critical integration of systems biology and synthetic biology approaches to accelerate the transition of terpenoid biomanufacturing from discovery to commercial scale.

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes was performed using bioinformatics tools, including HMMER and BLASTP, followed by phylogenetic analysis, gene structure analysis, conserved domain and motifs identification, cis-regulatory element prediction, protein–protein interaction analysis, and expression profiling using publicly available transcriptome data from UV-B treated A. annua six-week-old seedlings. We identified 24 AaOSC genes, classified into CAS, LAS, LUS, and unknown subfamilies. Phylogenetic analysis revealed evolutionary relationships with OSCs from other plant species. Gene structure analysis showed variations in exon–intron organization. Promoter analysis identified cis-regulatory elements related to light responsiveness, plant growth and development, hormone signaling, and stress response. Expression profiling revealed differential expression patterns of AaOSC genes under UV-B irradiation. This genome-wide characterization provides insights into the evolution and functional diversification of the OSC gene family in A. annua. The identified AaOSC genes and their regulatory elements lay the foundation for future studies aimed at manipulating triterpenoid biosynthesis for medicinal and biotechnological applications, particularly focusing on enhancing stress tolerance and artemisinin production.

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes was performed using bioinformatics tools, including HMMER and BLASTP, followed by phylogenetic analysis, gene structure analysis, conserved domain and motifs identification, cis-regulatory element prediction, protein-protein interaction analysis, and expression profiling using publicly available transcriptome data from UV-B treated A. annua six-week-old seedlings. We identified 24 AaOSC genes, classified into CAS, LAS, LUP, and unknown subfamilies. Phylogenetic analysis revealed evolutionary relationships with OSCs from other plant species. Gene structure analysis showed variations in exon-intron organization. Promoter analysis identified cis-regulatory elements related to light responsiveness, plant growth and development, hormone signaling, and stress response. Expression profiling revealed differential expression patterns of AaOSC genes under UV-B irradiation. This genome-wide characterization provides insights into the evolution and functional diversification of the OSC gene family in A. annua. The identified AaOSC genes and their regulatory elements lay the foundation for future studies aimed at manipulating triterpenoid biosynthesis for medicinal and biotechnological applications, particularly focusing on enhancing stress tolerance and artemisinin production.