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Complete biosynthetic pathway to the antidiabetic drug acarbose

Author

Listed:
  • Takeshi Tsunoda

    (Oregon State University)

  • Arash Samadi

    (Oregon State University)

  • Sachin Burade

    (Oregon State University)

  • Taifo Mahmud

    (Oregon State University)

Abstract

Acarbose is a bacterial-derived α-glucosidase inhibitor clinically used to treat patients with type 2 diabetes. As type 2 diabetes is on the rise worldwide, the market demand for acarbose has also increased. Despite its significant therapeutic importance, how it is made in nature is not completely understood. Here, we report the complete biosynthetic pathway to acarbose and its structural components, GDP-valienol and O-4-amino-(4,6-dideoxy-α-D-glucopyranosyl)-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose. GDP-valienol is derived from valienol 7-phosphate, catalyzed by three cyclitol modifying enzymes, whereas O-4-amino-(4,6-dideoxy-α-D-glucopyranosyl)-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose is produced from dTDP-4-amino-4,6-dideoxy-D-glucose and maltose by the glycosyltransferase AcbI. The final assembly process is catalyzed by a pseudoglycosyltransferase enzyme, AcbS, which is a homologue of AcbI but catalyzes the formation of a non-glycosidic C-N bond. This study clarifies all previously unknown steps in acarbose biosynthesis and establishes a complete pathway to this high value pharmaceutical.

Suggested Citation

  • Takeshi Tsunoda & Arash Samadi & Sachin Burade & Taifo Mahmud, 2022. "Complete biosynthetic pathway to the antidiabetic drug acarbose," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31232-4
    DOI: 10.1038/s41467-022-31232-4
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    References listed on IDEAS

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    1. Hundeep Kaur & Andrea Lakatos-Karoly & Ramona Vogel & Anne Nöll & Robert Tampé & Clemens Glaubitz, 2016. "Coupled ATPase-adenylate kinase activity in ABC transporters," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    2. Qinqin Zhao & Yuchang Luo & Xin Zhang & Qianjin Kang & Dan Zhang & Lili Zhang & Linquan Bai & Zixin Deng, 2020. "A severe leakage of intermediates to shunt products in acarbose biosynthesis," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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