Applied Microbiology and Biotechnology

, Volume 102, Issue 5, pp 2225–2234 | Cite as

Genomic-driven discovery of an amidinohydrolase involved in the biosynthesis of mediomycin A

  • Fengxian Sun
  • Shumei Xu
  • Fang Jiang
  • Weiying Liu
Applied genetics and molecular biotechnology


Clethramycin (1) and mediomycin A (2) belong to the linear polyene polyketide (LPP) family of antibiotics that exhibit potent antifungal activity. Structural similarities exist between 1 and 2, except that 2 contains an amino moiety substituted for the guanidino moiety. Herein, the draft genome sequence of Streptomyces mediocidicus ATCC23936, a strain which produces both 1 and 2, was obtained through de novo sequencing. Bioinformatic analysis of the genome revealed a clethramycin (cle) gene cluster that contained 25 open reading frames (orfs). However, amidinohydrolase for 2 formation was not found in the cle gene cluster. Further genomic analysis revealed an amidinohydrolase MedX, which can hydrolyse the guanidino form (1) into the amino form (2) via heterologous co-expression of the cle cluster in Streptomyces lividans or by in vitro catalysis. These results also suggest the feasibility of engineering novel LPPs for drug discovery by manipulating the biosynthetic machinery of S. mediocidicus.


Biosynthesis Clethramycin Mediomycin A Amidinohydrolase Linear polyene polyketides (LPPs) 



We thank Dr. Mei Ge, Shanghai Laiyi Center for Biopharmaceuticals R & D, for providing S. mediocidicus ATCC23936.

Funding information

This work was supported by grants from Tianjin science and technology plan projects (no. 16YFZCSY01000).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2017_8729_MOESM1_ESM.pdf (489 kb)
ESM 1 (PDF 489 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physiology and Pathophysiology, School of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  2. 2.Department of Pathogen Biology, School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

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