Analysis of the tunicamycin biosynthetic gene cluster of streptomyces chartreusis reveals new insights into tunicamycin production and immunity

Widdick, D., Royer, S. F., Wang, H. , Vior, N. M., Gomez-Escribano, J. P., Davis, B. G. and Bibb, M. J. (2018) Analysis of the tunicamycin biosynthetic gene cluster of streptomyces chartreusis reveals new insights into tunicamycin production and immunity. Antimicrobial Agents and Chemotherapy, 62(8), e00130-18. (doi: 10.1128/AAC.00130-18)

Abstract

The tunicamycin biosynthetic gene cluster of Streptomyces chartreusis consists of 14 genes (tunA to tunN) with a high degree of apparent translational coupling. Transcriptional analysis revealed that all of these genes are likely to be transcribed as a single operon from two promoters, tunp1 and tunp2. In-frame deletion analysis revealed that just six of these genes (tunABCDEH) are essential for tunicamycin production in the heterologous host Streptomyces coelicolor, while five (tunFGKLN) with likely counterparts in primary metabolism are not necessary, but presumably ensure efficient production of the antibiotic at the onset of tunicamycin biosynthesis. Three genes are implicated in immunity, namely, tunI and tunJ, which encode a two-component ABC transporter presumably required for export of the antibiotic, and tunM, which encodes a putative S-adenosylmethionine (SAM)-dependent methyltransferase. Expression of tunIJ or tunM in S. coelicolor conferred resistance to exogenous tunicamycin. The results presented here provide new insights into tunicamycin biosynthesis and immunity.

• Item Type: Articles
• Additional Information: This work was supported financially by the Biotechnological and Biological Sciences Research Council (BBSRC) grants BB/J006637/1 and BB/J009725/1 (“Understanding and exploiting tunicamycin [bio]synthesis to enable novel antibiotics and Inhibitors”) to M.J.B. and B.G.D. and by the BBSRC Institute Strategic Programme grant “Understanding and exploiting plant and microbial secondary metabolism” (grant BB/J004561/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wang, Dr Hua
• Authors: Widdick, D., Royer, S. F., Wang, H., Vior, N. M., Gomez-Escribano, J. P., Davis, B. G., and Bibb, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Antimicrobial Agents and Chemotherapy
• Publisher: American Society for Microbiology
• ISSN: 0066-4804
• ISSN (Online): 1098-6596
• Published Online: 27 July 2018
• Copyright Holders: Copyright © 2018 Widdick et al.
• First Published: First published in Antimicrobial Agents and Chemotherapy 62:e00130-18
• Publisher Policy: Reproduced under a Creative Commons License