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Front. Microbiol. | doi: 10.3389/fmicb.2018.00316

Bidirectional regulation of AdpAch in controlling the expression of scnRI and scnRII in the natamycin biosynthesis of Streptomyces chattanoogensis L10

Pin Yu1, 2, 3, Qing-Ting Bu1, 2, Yi-Li Tang1, 2, Xu-Ming Mao1, 2 and  Yong-Quan Li1, 2*
  • 1Institute of Pharmaceutical Biotechnology, Zhejiang University, China
  • 2Zhejiang Provincial Key Lab for Microbial Biochemistry and Metabolic Engineering, China
  • 3College of Life Sciences, Zhejiang University, China

AdpA, an AraC/XylS family protein, had been proved as a key regulator for secondary metabolism and morphological differentiation in Streptomyces griseus. Here, we identify AdpAch, an orthologue of AdpA, as a ‘higher level’ pleiotropic regulator of natamycin biosynthesis with bidirectional regulatory ability in Streptomyces chattanoogensis L10. DNase I footprinting revealed six AdpAch binding sites in the scnRI-scnRII intergenic region. Further analysis using the xylE reporter gene fused to the scnRI-scnRII intergenic region of mutated binding sites demonstrated that the expression of scnRI and scnRII were under the control of AdpAch. AdpAch showed a bi-stable regulatory ability where it firstly binds to the Site C and Site D to activate the transcription of the two pathway-specific genes, scnRI and scnRII, and then binds to other sites where it acts as an inhibitor. When Site A and Site F were mutated in vivo, the production of natamycin was increased by 21% and 25%, respectively. These findings indicated an autoregulatory mechanism where AdpAch serves as a master switch with bidirectional regulation for natamycin biosynthesis.

Keywords: Bidirectional regulation, ADPA, natamycin biosynthesis, Streptomyces chattanoogensis L10, pathway-specific gene

Received: 18 Dec 2017; Accepted: 09 Feb 2018.

Edited by:

Eung-Soo Kim, Inha University, South Korea

Reviewed by:

Yinhua Lu, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
Yasuo Ohnishi, The University of Tokyo, Japan  

Copyright: © 2018 Yu, Bu, Tang, Mao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yong-Quan Li, Zhejiang University, Institute of Pharmaceutical Biotechnology, Zhejiang University ,866 Yuhangtang Road,Hangzhou,China, Hangzhou, 310058, Zhejiang province, China, lyq@zju.edu.cn