Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster

doi:10.1007/s13659-025-00560-5

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (1): 7-7.DOI: 10.1007/s13659-025-00560-5

• Original Article • Previous Articles Next Articles

Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster

Yihong Li^1,2, Jie Fu^1,2, Hongmin Sun^1,2, Yu Du², Shuyi Si², Yuhuan Li^2,3, Xingxing Li^1,2, Jiandong Jiang^2,3, Bin Hong^1,2,4

1. CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
2. NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
3. CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
4. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China

Received:2025-08-11 Online:2026-03-25 Published:2026-02-14
Contact: Xingxing Li,E-mail:xingxingsf@163.com;Jiandong Jiang,E-mail:jiang.jdong@163.com;Bin Hong,E-mail:binhong69@hotmail.com
Supported by:
National Natural Science Foundation of China, 82273832, Bin Hong; 82104046, Hongmin Sun ; 32270106, Xingxing Li; 82404484, Yihong Li. CAMS Innovation Fund for Medical Sciences, 2021-I2M-1-070, Yihong Li,; 2021-I2M-1-029, Bin Hong. Postdoctoral Fellowship Program of CPSF, GZC20230291, Yihong Li.

Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster

Yihong Li^1,2, Jie Fu^1,2, Hongmin Sun^1,2, Yu Du², Shuyi Si², Yuhuan Li^2,3, Xingxing Li^1,2, Jiandong Jiang^2,3, Bin Hong^1,2,4

1. CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
2. NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
3. CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China;
4. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China

通讯作者: Xingxing Li,E-mail:xingxingsf@163.com;Jiandong Jiang,E-mail:jiang.jdong@163.com;Bin Hong,E-mail:binhong69@hotmail.com
基金资助:
National Natural Science Foundation of China, 82273832, Bin Hong; 82104046, Hongmin Sun ; 32270106, Xingxing Li; 82404484, Yihong Li. CAMS Innovation Fund for Medical Sciences, 2021-I2M-1-070, Yihong Li,; 2021-I2M-1-029, Bin Hong. Postdoctoral Fellowship Program of CPSF, GZC20230291, Yihong Li.

Abstract

Abstract: Omicsynins are a group of pseudo-tetrapeptides produced by Streptomyces sp. 1647, which exhibited potent anti-influenza A virus and anti-coronavirus activities. However, its biosynthesis mechanism of C-terminus reduction remains unknown. In this work, we explored two short-chain dehydrogenase/reductase (SDR) superfamily encoding genes in the omicsynin biosynthetic gene cluster (BGC) and confirmed the necessity of omnF, rather than omnG, in the biosynthesis of omicsynins through gene deletion in vivo. Subsequently, Feature-Based Molecular Networking (FBMN) analysis revealed three pseudo-tetrapeptides with C-terminal carboxyl group and four unexpected analogues encoded by the omicsynin BGC in the omnF reductase (R) domain knockout mutant strain. This led to the isolation and structural characterization of a group of novel pseudo-tripeptide compounds. Compared to the known omicsynins, these pseudo-tripeptides lack the second amino acid unit and the C-terminal aldehyde group, and consequently lose their anti-coronavirus activity. In conclusion, our work highlights the effectiveness of FBMN in unveiling cryptic analogues and clearly underscores the essential role of the R domain of OmnF in the biosynthesis of the C-terminal aldehyde warhead.

Key words: Omicsynins, FBMN, Pseudo-tripeptide, Reductase domain

摘要： Omicsynins are a group of pseudo-tetrapeptides produced by Streptomyces sp. 1647, which exhibited potent anti-influenza A virus and anti-coronavirus activities. However, its biosynthesis mechanism of C-terminus reduction remains unknown. In this work, we explored two short-chain dehydrogenase/reductase (SDR) superfamily encoding genes in the omicsynin biosynthetic gene cluster (BGC) and confirmed the necessity of omnF, rather than omnG, in the biosynthesis of omicsynins through gene deletion in vivo. Subsequently, Feature-Based Molecular Networking (FBMN) analysis revealed three pseudo-tetrapeptides with C-terminal carboxyl group and four unexpected analogues encoded by the omicsynin BGC in the omnF reductase (R) domain knockout mutant strain. This led to the isolation and structural characterization of a group of novel pseudo-tripeptide compounds. Compared to the known omicsynins, these pseudo-tripeptides lack the second amino acid unit and the C-terminal aldehyde group, and consequently lose their anti-coronavirus activity. In conclusion, our work highlights the effectiveness of FBMN in unveiling cryptic analogues and clearly underscores the essential role of the R domain of OmnF in the biosynthesis of the C-terminal aldehyde warhead.

关键词: Omicsynins, FBMN, Pseudo-tripeptide, Reductase domain

Yihong Li, Jie Fu, Hongmin Sun, Yu Du, Shuyi Si, Yuhuan Li, Xingxing Li, Jiandong Jiang, Bin Hong. Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster[J]. Natural Products and Bioprospecting, 2026, 16(1): 7-7.

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Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster

Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster

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