# Cytochrome P450 gene family: cross-pathway functional conservation, novel catalytic reactions, and synthetic biology-driven applications in plant secondary metabolism

**Authors:** Lang Chen, Yingying Zhao, Sujing He, Jialing Lei, Hongwei Li, Zhizhai Liu, Liang Zhang, Liwen Yang, Kuanping Deng, Runlan Wan, Delin Xu

PMC · DOI: 10.3389/fpls.2026.1765290 · Frontiers in Plant Science · 2026-02-20

## TL;DR

This review explores the role of cytochrome P450 enzymes in plant secondary metabolism and their potential for sustainable production of valuable compounds.

## Contribution

The paper proposes an integrated strategy combining CYP engineering and pathway optimization for enhanced metabolite production.

## Key findings

- CYPs are central to the biosynthesis of terpenoids, alkaloids, and flavonoids in plants.
- Transcriptional regulation and environmental signals significantly influence CYP gene expression.
- Synthetic biology and machine learning can advance CYP functional characterization and large-scale metabolite production.

## Abstract

Plant secondary metabolites play fundamental roles in plant defense and environmental adaptation, and possess extensive high-value applications in medicine, agriculture, and industrial biotechnology. The cytochrome P450 (CYPs) family occupies a central position in metabolic networks by catalyzing key reactions in the biosynthesis of terpenoids, alkaloids, and flavonoids. Although the role of CYPs in these pathways is well documented, their precise catalytic mechanisms and regulatory networks remain poorly characterized. In this review, we summarize recent advances in CYP classification, structural features, and catalytic diversity across plant species. We also analyze the transcriptional regulation and environmental signals that control CYP gene expression. Based on this synthesis, we propose an integrated strategy combining CYP enzyme engineering with metabolic pathway optimization to enhance the sustainable production of valuable secondary metabolites. Furthermore, we outline how CYP-centered approaches can improve the quality of medicinal plants and enable scalable bioreactor-based production. Interdisciplinary collaboration, supported by emerging technologies such as synthetic biology and machine learning, will be essential to overcome current limitations in CYP functional characterization, providing both mechanistic insights and practical solutions for the large-scale production of plant-derived natural products.

## Linked entities

- **Proteins:** CYP71B9 (cytochrome P450, family 71, subfamily B, polypeptide 9)

## Full-text entities

- **Genes:** LOC100780605 (cytochrome P450 71D8) [NCBI Gene 100780605] {aka CYP71D8}, CYP81F2 (cytochrome P450, family 81, subfamily F, polypeptide 2) [NCBI Gene 835828] {aka ''cytochrome P450, MJB24.3, MJB24_3, cytochrome P450, family 81, polypeptide 2}, WRKY33 (WRKY DNA-binding protein 33) [NCBI Gene 818429] {aka ATWRKY33, T19C21.4, T19C21_4, WRKY DNA-BINDING PROTEIN 33, WRKY DNA-binding protein 33}, MPK3 (mitogen-activated protein kinase 3) [NCBI Gene 823706] {aka ATMAPK3, ATMPK3, T6D9.4, mitogen-activated protein kinase 3}, WRKY18 (WRKY DNA-binding protein 18) [NCBI Gene 829308] {aka ARABIDOPSIS THALIANA WRKY DNA-BINDING PROTEIN 18, ATWRKY18, F11C18.16, WRKY DNA-binding protein 18}, P450 [NCBI Gene 542163], AP2 (Integrase-type DNA-binding superfamily protein) [NCBI Gene 829845] {aka AP22.49, AP22_49, APETALA 2, AtAP2, FL1, FLO2}, CYP82A2 (cytochrome P450 82A2-like) [NCBI Gene 100798546], CYP2B6 (cytochrome P450 family 2 subfamily B member 6) [NCBI Gene 1555] {aka CPB6, CYP2B, CYP2B7, CYPIIB6, EFVM, IIB1}, PAD3 (Cytochrome P450 superfamily protein) [NCBI Gene 822298] {aka CYP71B15, PHYTOALEXIN DEFICIENT 3}, MPK6 (MAP kinase 6) [NCBI Gene 818982] {aka ATMAPK6, ATMPK6, F18O19.10, MAP KINASE 6, MAP kinase 6, MAPK6}, LYST (lysosomal trafficking regulator) [NCBI Gene 1130] {aka CHS, CHS1, Mauve}, CYP71A13 (cytochrome P450 family 71 polypeptide) [NCBI Gene 817628] {aka T11J7.16, T11J7_16, cytochrome P450, family 71, polypeptide 13, subfamily A}, PPIG (peptidylprolyl isomerase G) [NCBI Gene 9360] {aka CARS-Cyp, CYP, SCAF10, SRCyp}, WRKY40 (WRKY DNA-binding protein 40) [NCBI Gene 844423] {aka ATWRKY40, F23A5.19, F23A5_19, WRKY DNA-binding protein 40}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}
- **Diseases:** toxicity (MESH:D064420), infection (MESH:D007239), atherosclerosis (MESH:D050197), Alzheimer's disease (MESH:D000544), cancer (MESH:D009369), inflammatory (MESH:D007249), HL (MESH:C538324)
- **Chemicals:** oleanolic acid (MESH:D009828), Flavonoid (MESH:D005419), amorpha-4,11-diene (MESH:C515348), diterpene (MESH:D004224), miltiradiene (MESH:C573600), Indole (MESH:C030374), baicalein (MESH:C006680), JA (MESH:C011006), saponin (MESH:D012503), cyclic ether (MESH:D004988), baicalin (MESH:C038044), loganic acid (MESH:C002947), flavones (MESH:D047309), glycinol (MESH:C540862), anthocyanin (MESH:D000872), A (MESH:D001151), camptothecin (MESH:D002166), taxane (MESH:C080625), hydrogen (MESH:D006859), alcohols (MESH:D000438), glyceollin (MESH:C017343), Isopentenyl Pyrophosphate (MESH:C004809), tryptophan (MESH:D014364), lactone (MESH:D007783), tropane alkaloid (MESH:D014326), artemisinic acid (MESH:C047721), secologanic acid (MESH:C000628855), sesquiterpenes (MESH:D012717), sterol (MESH:D013261), hyoscyamine (MESH:D064692), jasmonoyl-isoleucine (MESH:C532883), isoquinoline (MESH:C039109), ATP (MESH:D000255), beta-amyrin (MESH:C036380), pentacyclic triterpene (MESH:D053978), Lignin (MESH:D008031), FMN (MESH:D005486), Farnesyl Pyrophosphate (MESH:C004808), PPT (MESH:C081552), triptolide (MESH:C001899), phenylalanine (MESH:D010649), triterpene (MESH:D014315), FAD (MESH:D005182), GA (MESH:C556862), 3,9-dihydroxypterocarpan (MESH:C042060), gramine (MESH:C007884), camalexin (MESH:C102405), norbelladine (MESH:C000629946), daidzein (MESH:C004742), Quillaic acid (MESH:C005564), carbohydrate (MESH:D002241), monoterpenes (MESH:D039821), fatty acid (MESH:D005227), Geranyl Pyrophosphate (MESH:C015234), 7-deoxyloganic acid (MESH:C432876), salvinone (MESH:C061456), delphinidin- (MESH:C017185), shikimate (MESH:C000723335), amino acid (MESH:D000596), heme (MESH:D006418)
- **Species:** Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Rauvolfia serpentina (devilpepper, species) [taxon 4060], Hordeum vulgare (barley, species) [taxon 4513], Glycyrrhiza glabra (species) [taxon 49827], Medicago truncatula (barrel medic, species) [taxon 3880], Solanum tuberosum (potatoes, species) [taxon 4113], Camellia sinensis (black tea, species) [taxon 4442], Salvia (sages, genus) [taxon 21880], Pyrus (pears, genus) [taxon 3766], Homo sapiens (human, species) [taxon 9606], Camptotheca acuminata (species) [taxon 16922], Zea mays (maize, species) [taxon 4577], Dendrobium nobile (species) [taxon 94219], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Eschscholzia californica (California poppy, species) [taxon 3467], Glycyrrhiza uralensis (Chinese licorice, species) [taxon 74613], Populus trichocarpa (black cottonwood, species) [taxon 3694], Tripterygium wilfordii (species) [taxon 458696], Solanum lycopersicum (tomato, species) [taxon 4081], Dendrobium chrysotoxum (species) [taxon 161865], Epimedium sagittatum (species) [taxon 253616], Panax ginseng (Asiatic ginseng, species) [taxon 4054], Ganoderma lucidum (species) [taxon 5315], Artemisia annua (sweet Annie, species) [taxon 35608], Panax (genus) [taxon 4053], Scutellaria baicalensis (Baikal skullcap, species) [taxon 65409], Dendrobium huoshanense (species) [taxon 154293], Gossypium hirsutum (American cotton, species) [taxon 3635], Vitex agnus-castus (chasteberry, species) [taxon 54477], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Ocimum tenuiflorum (holy basil, species) [taxon 204149], Morus alba (white mulberry, species) [taxon 3498], Glycine max (soybean, species) [taxon 3847]
- **Mutations:** A82F, T268A, L188Q, F87V, L437Q
- **Cell lines:** SiF3'5'H — Mus musculus (Mouse), Hybridoma (CVCL_XB15)

## Full text

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## Figures

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## References

87 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963337/full.md

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Source: https://tomesphere.com/paper/PMC12963337