Research Article Open Access
Research Article Open Access
Aiman et al., J Proteomics Bioinform 2018, 11:1
DOI: 10.4172/jpb.1000460
Journal of
Proteomics & Bioinformatics
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ISSN: 0974-276X
Volume 11(1) 001-007 (2018) - 1
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
*Corresponding author: Asifullah Khan, Assistant Professor, Department of
Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan, Tel: +92-
937-929122; E-mail: asif@awkum.edu.pk
Received December 07, 2017; Accepted January 10, 2018; Published January 17,
2018
Citation: Aiman S, Shehroz M, Munir M, Gul S, Shah M, et al. (2018) Species-Wide
Genome Mining of Pseudomonas putida for Potential Secondary Metabolites and
Drug-Like Natural Products Characterization. J Proteomics Bioinform 11: 001-007. doi:
10.4172/jpb.1000460
Copyright: © 2018 Aiman S, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Keywords: Biosynthetic gene cluster; Secondary metabolites;
Pseudomonas putida; Bacterial genomics
Introduction
Microbial secondary metabolites are small organic compounds
play important role in the survival of microbial culture and ecological
interaction with other organisms [1]. Microbial natural products
are used as agricultural, dietary and pharmaceutical agents. Tese
include nonribosomal peptides (NRPs), polyketides (PKs), post-
translationally modifed peptides (RiPPs), ribosomally synthesized
compounds, saccharides, terpenoids and some hybrids natural
products. Te biosynthesis of these secondary metabolites are directed
by group of genes physically located within a single locus on microbial
chromosomal and plasmid DNA termed as Biosynthetic Gene Clusters
(BGCs). Tese clusters allow the concerted expression of necessary
biosynthetic, regulatory enzymes and transporter proteins require
for biosynthesis, mechanism of action and transport of secondary
metabolites [2]. Te rich genetic diversity of microbial BGCs due to
evolutionary basis eventually cause high chemical diversity in their
underlie coding secondary metabolites [3,4].
Te P. putida is a gram-negative bacterium typically colonizes at soil
and aquatic habitats. Te strains of this species exhibit wide metabolic
versatility driving their adaptability to diverse habitats. Te P. putida
strains are important for the biosynthesis of variety of biotechnological
signifcant natural products by heterologous expression of diverse
biosynthetic pathways [5]. P. putida ofer several particular advantages
with respect to natural product biosynthesis, notably a versatile
intrinsic metabolism with diverse enzymatic capacities and outstanding
tolerance to xenobiotics. Terefore, P. putida strains are potential source
of antimicrobial agents and implement in recombinant biosynthesis of
valuable natural products [5,6].
Te decreasing cost of genome-level DNA sequencing
due to technological advancement in the form of next-
generation sequencing allowed to understand the ecological diversity
and dynamic functionality of microbial communities with increase
resolution. Nowadays, these fast genome sequencing along with
advance bioinformatics resources transformed the secondary
Species-Wide Genome Mining of Pseudomonas putida for Potential
Secondary Metabolites and Drug-Like Natural Products Characterization
Sara Aiman, Muhammad Shehroz, Mehwish Munir, Sahib Gul, Mohibullah Shah and Asifullah Khan
*
Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan-23200, Pakistan
Abstract
The gram negative bacteria species of Pseudomonas putida (P. putida) are important for heterologous expression
of diverse biosynthetic pathways and numerous secondary metabolites biosynthesis. The genes code for such
secondary metabolites biosynthetic proteins are organized in microbial genomes as clusters to bring the concerted
expression of entire biosynthetic machinery. The complete and whole genome sequences of more than ffty different
strains available in public DNA sequences databases provide an excellent opportunity to investigate the genetically
encoded secondary metabolites potential of ecologically diverse P. putida strains. We implement the advance
bioinformatics resources to annotate the so far available P. putida strains genomes for biosynthetic gene clusters
(BGCs) and underlie secondary metabolites chemical scaffolds. The P. puida strains are found to harbor genomic
signatures coding the molecular machinery for diverse secondary metabolites biosynthesis. The corresponding
BGCs of these metabolites are found to be uniquely distributed across different P. putida strains speculate their role
toward strain's ecological competency acquirement. The chemoinformatics dereplication and DrugBank database
searching revealed the chemical mimicry of one putative metabolite with 2, 3, Dihydroxybenzoylserine, that mediates
an antibiotic iron depletion along with human neutrophil lipocalin during innate immune response.
metabolites discovery approaches towards more rational and predictive
directions [7]. Moreover, the organization of BGCs as single locus on
bacterial chromosomal and plasmid DNA actually eased these genomic
motifs confdent in silico predictions based on fundamental principles
of bioinformatics [8]. However, still the genome-guided microbial
secondary metabolites discovery and knowledge is limited compare to
bioassay screening. In this study, we adopted multiple computational
biology resources to mine all publically available whole genome
sequences of P. putida strains to elucidate the secondary metabolites
coding potential of this species. Te chemical scafolds of putative
secondary metabolites as identifed are further evaluated for drug-like
potential using chemoinformatics resources.
Material and Methods
Genome sequences retrieval
Te complete and partial genomes assemblies of 58 diferent stains
and isolates of P. putida are retrieved from NCBI Genbank [9] and
Integrated Microbial Genome (IMG) databases [10]. Te data retrieval
was made in March 2016.
Secondary metabolites prediction
Several prediction models are implemented in bioinformatics
resources for putative identifcation of BGCs responsible for