Comparative functional genomics of the acarbose producers reveals potential targets for metabolic engineering.

ABSTRACT: The α-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp. SE50 and used widely for the treatment of type-2 diabetes. Compared with the wild-type SE50, a high-yield derivative Actinoplanes sp. SE50/110 shows 2-fold and 3-7-fold improvement of acarbose yield and acb cluster transcription, respectively. The genome of SE50 was fully sequenced and compared with that of SE50/110, and 11 SNVs and 4 InDels, affecting 8 CDSs, were identified in SE50/110. The 8 CDSs were individually inactivated in SE50. Deletions of ACWT_4325 (encoding alcohol dehydrogenase) resulted in increases of acarbose yield by 25% from 1.87 to 2.34 g/L, acetyl-CoA concentration by 52.7%, and PEP concentration by 22.7%. Meanwhile, deletion of ACWT_7

SUBMITTER: Xie H 

PROVIDER: S-EPMC6350373 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature