2. Academic Validation
  3. Reticuline isomerase AKR1B1 with aldo-keto reductase activity and detoxification function from the insect Blaps rhynchopetera

Reticuline isomerase AKR1B1 with aldo-keto reductase activity and detoxification function from the insect Blaps rhynchopetera

  • Int J Biol Macromol. 2026 Mar:352:151224. doi: 10.1016/j.ijbiomac.2026.151224.
Lamei Zhang 1,  Shengwen Zhou 2,  Xizhe Yang 3,  James Mwangi 2,  Kaixun Cao 4,  Chengchen Zhang 4,  Ping Meng 5,  Ziyi Wang 4,  Min Zhao 6,  Lei Shi 7,  Qiumin Lu 8
Affiliations

Affiliations

  • 1 Yunnan Key Laboratory of Breeding and Utilization of Resource Insects, Key Laboratory of Breeding and Utilization of Resource Insects of National Forestry and Grassland Administration, Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming, 650224, China; Institute of Quality Standards and Detection Technology, Yunnan Academy of Agricultural Sciences, China.
  • 2 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No. 17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Yunnan Key Laboratory of Breeding and Utilization of Resource Insects, Key Laboratory of Breeding and Utilization of Resource Insects of National Forestry and Grassland Administration, Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming, 650224, China.
  • 4 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No. 17 Longxin Road, Kunming, Yunnan, 650201, China.
  • 5 Key Laboratory of Cardiovascular Disease of Yunnan Province, Department of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 6 Yunnan Key Laboratory of Breeding and Utilization of Resource Insects, Key Laboratory of Breeding and Utilization of Resource Insects of National Forestry and Grassland Administration, Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming, 650224, China. Electronic address: [email protected].
  • 7 Yunnan Key Laboratory of Breeding and Utilization of Resource Insects, Key Laboratory of Breeding and Utilization of Resource Insects of National Forestry and Grassland Administration, Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming, 650224, China. Electronic address: [email protected].
  • 8 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No. 17 Longxin Road, Kunming, Yunnan, 650201, China; Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan, 650106, China. Electronic address: [email protected].
PMID: 41791543 DOI: 10.1016/j.ijbiomac.2026.151224
Abstract

Herbivorous insects have evolved a dual adaptive strategy when exposed to small-molecule compounds such as Alkaloids. They can utilize certain compounds to support growth and development, while detoxifying harmful ones through endogenous Enzymes. Multiple Enzymes, including aldo-keto reductases (AKRs) and Cytochrome P450 enzymes, participate in these processes. Currently, the isomerase responsible for producing reticuline has only been identified in Plants, with no reports of its existence in Animals or insects to date. In light of this, from the transcriptome of Blaps rhynchopetera, we identified a novel aldo-keto reductase, AKR1B1, with diverse biological functions. This study demonstrates for the first time in vitro that AKR1B1 catalyzes the conversion of (S)-reticuline to (R)-reticuline, suggesting its dual role as both an aldo-keto reductase and an isomers enzyme. Virtual screening revealed tiaprofenic acid and pipemidic acid as small-molecule inhibitors of AKR1B1, effectively suppressing its catalytic activity toward (S)-reticuline. Antibody-based localization experiments demonstrated the highest expression levels of AKR1B1 in adults and midgut tissues, with minimal expression in eggs and muscle tissues. Furthermore, Insecticide induction experiments confirmed AKR1B1's detoxification role in B. rhynchopetera. These findings establish AKR1B1 as a novel and critical player in insect compound metabolism and detoxification. This discovery provides new targets for developing insect-derived bifunctional Enzymes for drug development and detoxification research, offering profound insights into the physiological mechanisms of insects.

Keywords

AKR1B1; Blaps rhynchopetera; Catalytic function; Detoxification; Small-molecule inhibitors.

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