Genomic characterization of a new endophytic Streptomyces kebangsaanensis identifies biosynthetic pathway gene clusters for novel phenazine antibiotic production

Juwairiah Remali, Nurul Izzah Mohd Sarmin, Chyan Leong Ng, John J.L. Tiong, Wan Mohd Aizat Wan Kamaruddin, Loke Kok Keong, Noraziah Mohamad Zin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background. Streptomyces are well known for their capability to produce many bioac- tive secondary metabolites with medical and industrial importance. Here we report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy) carbonyl) phenazine-1-carboxylic acid (HCPCA) extracted from Streptomyces kebangsaanensis, an endophyte isolated from the ethnomedicinal Portulaca oleracea. Methods. The HCPCA chemical structure was determined using nuclear magnetic resonance spectroscopy. We conducted whole genome sequencing for the identification of the gene cluster(s) believed to be responsible for phenazine biosynthesis in order to map its corresponding pathway, in addition to bioinformatics analysis to assess the potential of S. kebangsaanensis in producing other useful secondary metabolites. Results. The S. kebangsaanensis genome comprises an 8,328,719 bp linear chromosome with high GC content (71.35%) consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We identified 24 gene clusters involved in polyketide, nonribosomal peptide, terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster predicted to be responsible for phenazine biosynthesis. Discussion. The HCPCA phenazine structure was hypothesized to derive from the combination of two biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2-diol, originated from the shikimic acid pathway. The identifica- tion of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics. Additionally, these findings confirm the potential of S. kebangsaanensis for producing various antibiotics and secondary metabolites.

Original languageEnglish
Article numbere3738
JournalPeerJ
Volume2017
Issue number11
DOIs
Publication statusPublished - 1 Jan 2017

Fingerprint

phenazines
Biosynthetic Pathways
Streptomyces
Multigene Family
multigene family
biochemical pathways
Genes
antibiotics
Anti-Bacterial Agents
genomics
Biosynthesis
Metabolites
carboxylic acids
biosynthesis
secondary metabolites
Portulaca
Shikimic Acid
rRNA Operon
Genome
Endophytes

Keywords

  • Genomic
  • Phenazine
  • S. kebangsaanensis
  • Secondary metabolites

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genomic characterization of a new endophytic Streptomyces kebangsaanensis identifies biosynthetic pathway gene clusters for novel phenazine antibiotic production. / Remali, Juwairiah; Sarmin, Nurul Izzah Mohd; Ng, Chyan Leong; Tiong, John J.L.; Wan Kamaruddin, Wan Mohd Aizat; Keong, Loke Kok; Mohamad Zin, Noraziah.

In: PeerJ, Vol. 2017, No. 11, e3738, 01.01.2017.

Research output: Contribution to journalArticle

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abstract = "Background. Streptomyces are well known for their capability to produce many bioac- tive secondary metabolites with medical and industrial importance. Here we report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy) carbonyl) phenazine-1-carboxylic acid (HCPCA) extracted from Streptomyces kebangsaanensis, an endophyte isolated from the ethnomedicinal Portulaca oleracea. Methods. The HCPCA chemical structure was determined using nuclear magnetic resonance spectroscopy. We conducted whole genome sequencing for the identification of the gene cluster(s) believed to be responsible for phenazine biosynthesis in order to map its corresponding pathway, in addition to bioinformatics analysis to assess the potential of S. kebangsaanensis in producing other useful secondary metabolites. Results. The S. kebangsaanensis genome comprises an 8,328,719 bp linear chromosome with high GC content (71.35{\%}) consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We identified 24 gene clusters involved in polyketide, nonribosomal peptide, terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster predicted to be responsible for phenazine biosynthesis. Discussion. The HCPCA phenazine structure was hypothesized to derive from the combination of two biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2-diol, originated from the shikimic acid pathway. The identifica- tion of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics. Additionally, these findings confirm the potential of S. kebangsaanensis for producing various antibiotics and secondary metabolites.",
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