Acarbose May Function as a Competitive Exclusion Agent for the Producing Bacteria

• Published in: ACS chemical biology Vol. 18; no. 2; pp. 367 - 376
• Main Authors: Tanoeyadi, Samuel, Tsunoda, Takeshi, Ito, Takuya, Philmus, Benjamin, Mahmud, Taifo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.02.2023
• Subjects: Acarbose; Actinobacteria - metabolism; alpha-Amylases - metabolism; Bacterial Proteins - metabolism; Diabetes Mellitus, Type 2; Humans
• DOI: 10.1021/acschembio.2c00795
• ISSN: 1554-8929; 1554-8937

Acarbose is a well-known microbial specialized metabolite used clinically to treat type 2 diabetes. This natural pseudo-oligosaccharide (PsOS) shows potent inhibitory activity toward various glycosyl hydrolases, including α-glucosidases and α-amylases. While acarbose and other PsOSs are produced by many different bacteria, their ecological or biological role in microbial communities is still an open question. Here, we show that several PsOS-producing actinobacteria, i.e., Actinoplanes sp. SE50/110 (acarbose producer), Streptomyces glaucescens GLA.O (acarbose producer), and Streptomyces dimorphogenes ATCC 31484 (trestatin producer), can grow in the presence of acarbose, while the growth of the non-PsOS-producing organism Streptomyces coelicolor M1152 was suppressed when starch is the main source of energy. Further investigations using recombinant α-amylases from S. coelicolor M1152 and the PsOS-producing actinobacteria revealed that the S. coelicolor α-amylase was inhibited by acarbose, whereas those from the PsOS-producing bacteria were not inhibited by acarbose. Bioinformatic and protein modeling studies suggested that a point mutation in the α-amylases of the PsOS-producing actinobacteria is responsible for the resistance of those enzymes toward acarbose. Converting the acarbose-resistant α-amylase AcbE to its A304H variant diminished its acarbose-resistance property. Taken together, the results suggest that acarbose is used by the producing bacteria as a competitive exclusion agent to suppress the growth of other microorganisms in their natural environment, while the producing organisms equip themselves with α-amylase variants that are resistant to acarbose.