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Applied Microbiology and Biotechnology

, Volume 102, Issue 13, pp 5635–5643 | Cite as

Enhancement of A82846B yield and proportion by overexpressing the halogenase gene in Amycolatopsis orientalis SIPI18099

  • Wei-Yan Wang
  • Song-Bai Yang
  • Yuan-Jie Wu
  • Xiao-Fang Shen
  • Shao-Xin Chen
Applied genetics and molecular biotechnology
  • 103 Downloads

Abstract

The glycopeptide antibiotic A82846B (chloroeremomycin) produced by Amycolatopsis orientalis is the precursor of the semi-synthetic antibiotic oritavancin. However, during the industrial production of A82846B, two major impurities, A82846A (63.6%) and A82846C (12%) which are structurally similar to A82846B (24.4%), are also produced. In this study, to improve the ratio of A82846B to A and C, the genes encoding halogenase in A82846B and vancomycin synthesis were integrated into A. orientalis SIPI18099 to test their halogenation ability, respectively. The results indicated that chal from the A82846B biosynthesis pathway was more efficient in reducing A and C factors. Moreover, by increasing the chal copy number, the proportion of A and C were gradually reduced while the titer and proportion of A82846B were improved. In a scaled-up industrial process, the proportion of A and C were decreased to 11.6% and 0.2% in the recombinant strain A.orientalis chal-3 with three gene copies of chal and the titers of A82846B (2.2 g/L) has increased by 2.8-folds compared to 780 mg/L produced by the parental strain, suggesting that the recombinant strain was suitable for the industrial production of A82846B with lower impurities.

Keywords

A82846B Vancomycin Amycolatopsis orientalis Halogenase gene Overexpression 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

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Copyright information

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

Authors and Affiliations

  • Wei-Yan Wang
    • 1
  • Song-Bai Yang
    • 1
  • Yuan-Jie Wu
    • 1
  • Xiao-Fang Shen
    • 1
  • Shao-Xin Chen
    • 1
  1. 1.Shanghai Institute of Pharmaceutical IndustryShanghaiChina

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