Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity
Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 cata...
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KeAi Communications Co., Ltd.
2024-06-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24000401 |
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| author | Xin Zhang Qungang Huang Ziyue Guo Feifei Cai Qianjin Kang Linquan Bai |
| author_facet | Xin Zhang Qungang Huang Ziyue Guo Feifei Cai Qianjin Kang Linquan Bai |
| author_sort | Xin Zhang |
| collection | DOAJ |
| description | Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towards α-amylase than acarbose. Recombinant AcbE mainly catalyzed the formation of two new compounds, namely acarstatins A and B, using acarbose as substrate. Using high-resolution mass spectrometry, nuclear magnetic resonance, and glycosidase hydrolysis, we elucidated their chemical structures as O-α-d-maltosyl-(1 → 4)-acarbose and O-α-d-maltotriosyl-(1 → 4)-acarbose, respectively. Acarstatins A and B exhibited 1584- and 1478-fold greater inhibitory activity towards human salivary α-amylase than acarbose. Furthermore, both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis. Therefore, acarstatins A and B have great potential as candidate therapeutic agents for T2DM. |
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| issn | 2405-805X |
| language | English |
| last_indexed | 2025-03-21T21:16:21Z |
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| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-22356a4010b64499a611e5260f5cf45b2024-05-29T05:02:32ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2024-06-0192359368Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activityXin Zhang0Qungang Huang1Ziyue Guo2Feifei Cai3Qianjin Kang4Linquan Bai5State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China; Corresponding author.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China; College of Life Science, Tarim University, Alar, 843300, China; Corresponding author. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towards α-amylase than acarbose. Recombinant AcbE mainly catalyzed the formation of two new compounds, namely acarstatins A and B, using acarbose as substrate. Using high-resolution mass spectrometry, nuclear magnetic resonance, and glycosidase hydrolysis, we elucidated their chemical structures as O-α-d-maltosyl-(1 → 4)-acarbose and O-α-d-maltotriosyl-(1 → 4)-acarbose, respectively. Acarstatins A and B exhibited 1584- and 1478-fold greater inhibitory activity towards human salivary α-amylase than acarbose. Furthermore, both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis. Therefore, acarstatins A and B have great potential as candidate therapeutic agents for T2DM.http://www.sciencedirect.com/science/article/pii/S2405805X24000401Acarbose analogsα-amylase inhibitory activityActinoplanes sp.Transglycosylase |
| spellingShingle | Xin Zhang Qungang Huang Ziyue Guo Feifei Cai Qianjin Kang Linquan Bai Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity Synthetic and Systems Biotechnology Acarbose analogs α-amylase inhibitory activity Actinoplanes sp. Transglycosylase |
| title | Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity |
| title_full | Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity |
| title_fullStr | Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity |
| title_full_unstemmed | Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity |
| title_short | Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity |
| title_sort | acarbose glycosylation by acbe for the production of acarstatins with enhanced α amylase inhibitory activity |
| topic | Acarbose analogs α-amylase inhibitory activity Actinoplanes sp. Transglycosylase |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X24000401 |
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