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

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

doi:10.7717/peerj.3738

Juwairiah Remali, Noraziah Mohamad Zin + Show 5 more

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https://doi.org/10.7717/peerj.3738

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Abstract

BackgroundStreptomyces are well known for their capability to produce many bioactive 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.MethodsThe 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.ResultsThe 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.DiscussionThe 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 identification 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.

Highlights

Streptomyces are Gram positive, filamentous saprophytes known for their roles in producing various secondary metabolites important for medicinal therapies (Hopwood, 2007; Kieser, 2000)
Streptomyces kebangsaanensis represents a novel endophyte isolated from the ethnomedical plant, Portulaca oleracea Linn, known in Malaysia as ‘Gelang pasir’, that was demonstrated to have medicinal and pharmaceutical properties such as antiseptic and anti-inflammatory activities (Lim & Quah, 2007; Sarmin et al, 2013)
It has been found to produce the bioactive compound phenazine1-carboxylic acid, which was shown to have antibacterial, anticancer, antiparasitic, and antiviral properties (Laursen & Nielsen, 2004; Sarmin et al, 2013). This suggests that S. kebangsaanensis represents an untapped source of bioactive compounds such as phenazines that might be potentially further utilised

Summary

Introduction

Streptomyces are Gram positive, filamentous saprophytes known for their roles in producing various secondary metabolites important for medicinal therapies (Hopwood, 2007; Kieser, 2000). It has been found to produce the bioactive compound phenazine1-carboxylic acid (known as tubermycin B), which was shown to have antibacterial, anticancer, antiparasitic, and antiviral properties (Laursen & Nielsen, 2004; Sarmin et al, 2013) This suggests that S. kebangsaanensis represents an untapped source of bioactive compounds such as phenazines that might be potentially further utilised. The identification of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics These findings confirm the potential of S. kebangsaanensis for producing various antibiotics and secondary metabolites

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