Identification and Functional Analysis of the Nocardithiocin Gene Cluster in Nocardia pseudobrasiliensis

PLoS One. 2015 Nov 20;10(11):e0143264. doi: 10.1371/journal.pone.0143264. eCollection 2015.


Nocardithiocin is a thiopeptide compound isolated from the opportunistic pathogen Nocardia pseudobrasiliensis. It shows a strong activity against acid-fast bacteria and is also active against rifampicin-resistant Mycobacterium tuberculosis. Here, we report the identification of the nocardithiocin gene cluster in N. pseudobrasiliensis IFM 0761 based on conserved thiopeptide biosynthesis gene sequence and the whole genome sequence. The predicted gene cluster was confirmed by gene disruption and complementation. As expected, strains containing the disrupted gene did not produce nocardithiocin while gene complementation restored nocardithiocin production in these strains. The predicted cluster was further analyzed using RNA-seq which showed that the nocardithiocin gene cluster contains 12 genes within a 15.2-kb region. This finding will promote the improvement of nocardithiocin productivity and its derivatives production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • DNA Primers
  • Genetic Complementation Test
  • Genome, Bacterial
  • Mass Spectrometry
  • Multigene Family*
  • Mycobacterium / drug effects
  • Nocardia / genetics*
  • Nocardia / metabolism
  • Peptides / chemistry
  • Peptides, Cyclic / genetics*
  • Peptides, Cyclic / metabolism*
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Species Specificity
  • Spectrophotometry, Ultraviolet
  • Thiazoles / metabolism*


  • Anti-Bacterial Agents
  • DNA Primers
  • Peptides
  • Peptides, Cyclic
  • Thiazoles
  • nocardithiocin

Grant support

This work was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT),, #25305012, to TG. The funder had no role in this study.