Functional analysis of down-regulated CYP6AE gene clusters involved in the insecticidal mechanism of lycorine against Spodoptera litura

  • Pest Manag Sci. 2026 Jun 20. doi: 10.1002/ps.71003.
Yingdan Xiao  1 ,  Xue Yang  1 ,  Jianqiu Liu  1 ,  Shaopeng Hao  1 ,  Yajing Xu  2 ,  Yue Chen  1 ,  Huizhen Guo  1 ,  Qingyou Xia  1 ,  Marian R Goldsmith  3 ,  Guy Smagghe  4  5 ,  Kazuei Mita  1
Affiliations
  • 1. Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Chongqing Technology Innovation Center of Breeding, Biological Science Research Center, Southwest University, Chongqing, China.
  • 2. Department of Neurosurgery and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 3. Department of Biological Sciences, College of the Environment and Life Sciences, University of Rhode Island, Kingston, RI, USA.
  • 4. Institute of Entomology, Guizhou University, Guiyang, China.
  • 5. Department of Biology, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
PMID: 42322590 DOI: 10.1002/ps.71003
Abstract

Background: Plants have evolved abundant defensive secondary metabolites to resist insect herbivores. Lycorine is an alkaloid with insecticidal activity from Amaryllidaceae plants, which the destructive pest Spodoptera litura naturally avoids. Cytochrome P450 enzymes are central to xenobiotic detoxification in insects, but the mechanism by which lycorine acts against S. litura remains unknown. This study aimed to reveal the toxic mechanism of lycorine focusing on P450-mediated detoxification.

Results: Lycorine exhibited substantial toxicity to first-instar S. litura larvae (LD50 = 0.55 μg larva-1). Subsequently, when fifth-instar larvae were exposed to a sublethal dose (LD30) of lycorine, Lyc disrupted metabolic pathways, damaged Malpighian tubules, and induced oxidative stress. Furthermore, lycorine strongly repressed a CYP6AE gene cluster (CYP6AE47, CYP6AE50, CYP6AE70, CYP6AE138 and CYP6AE139) and decreased total P450 activity to 45% in the Malpighian tubules. RNAi co-silencing of these cluster genes increased larval mortality (+30%) under lycorine treatment. Finally, molecular docking and microscale thermophoresis analyses further confirmed direct binding between Lyc and this CYP6AE gene cluster, with the strongest affinity observed for CYP6AE47 (Kd = 518.5 nM). A key residue, ARG170, may be vital for the interaction between Lyc and CYP6AE47.

Conclusions: These results demonstrate that the insecticidal mechanism of Lyc involves suppressing the expression and function of a CYP6AE gene cluster, thereby impairing detoxification capacity, which leads to Lyc accumulation and larval mortality. Elucidation of the detoxification system-targeted mechanism for this plant-derived compound provides a foundation for developing novel, sustainable pest management strategies against S. litura and potentially Other noctuid pests. © 2026 Society of Chemical Industry.

Keywords
Malpighian tubule; Spodoptera litura; action mechanism; cytochrome P450; lycorine; oxidative stress.
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