Bacterial therapeutic agents and huge number of drugs on

Bacterial natural systems are varied in different size and some
have very small genomes. The existence and important roles of
ultramicrobacteria are confirmed in various literature (1). It is clear that
ultramicrobacteria impact on microbial genomics.

However, a very large gap exists between the ultramicrobacteria , throughput of
sequencing and the rate of discovery of novel pathways involved in secondary
metabolism predominantly because of the lack
of research work and computational tools (2).

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Bacterial secondary metabolites have many different physiochemical,
biological properties and have important role in the development of novel
medicines, antitumor drugs and immunosuppressive, antiparasitics drugs. They
are the main source for new therapeutic agents and huge number of drugs on the
market are derived from natural products over the 30 years (3). Most
antibiotics, such as penicillin, erythromycin or tetracycline, and also other
drugs like acarbose (anti-diabetic), artemisinin (anti-malarial), tacrolimus or
cyclosporins (immunosuppressants) are derived from natural products(1) .This
Secondary metabolites usually comprise various chemical moieties, such as
polyketide backbones, amino acid derivatives and sugars.

non-ribosomal peptide synthetase (NRPS) and Polyketide synthase
(PKS) are major enzymes involved in secondary metabolite. PKS synthesized Polyketides and fall into

Three groups type I, II, and III

For novel compound discovery, microbiologists are increasingly
relying on sequencing genomes of a wide variety of microbes (the study of a
microbial community without the need of cultivation in the laboratory) that describes
biodiversity and biochemical potential of a microbial community and full
sequence information.  There is
limitation to identify microorganism through cultured isolates (4) .the metagenomics
approaches have been used to solve this limitation,

So mining of
genomes has become an increasingly powerful, scalable, and economically
accessible tool for the natural
product research, biosynthesis and drug discovery. However, only few
studies were investigated metagenomes databases for biosynthesis of natural
product and much more work is
needed in this area.

Diverse microbial communities in subsurface environments including
water systems exhibit extraordinary phylogenetic diversity and metabolic
complexity that has only recently become apparent using culture-independent
sequencing-based analytics 5

Plenty of tools are
available for genome mining and also several computational tools have been developed for detection of secondary metabolite
biosynthetic pathways
in sequenced fungal or bacterial genomes and some of these tools are able to
predict substrate specificity of polymerization enzymes, generate
approximations for products’ 3D structures, and more.

In this paper we used antiSMASH for Identification and analysis genomic
of biosynthetic gene clusters.We used antiSMASH, version 4.0, which has undergone numerous improvements
(3). One of the main reasons we select antiSMASH is that it allow us to run
other analyses such as substrate specificity, homologous sequence, predicted
structure and more in addition to gene cluster identification

In the current study we analysis metagenomics of surface water that
passed through a 0.1-?m

Membrane filter to extract DNA, metagenome sequencing, assembly,
and then using the Anti-SMASH and NAPDOS. In overall this study aims to (i) mining
of metagenomes  in ultra-small bacteria, sequence
generation (ii) to proof present of secondary metabolite in ultra-small
bacterial cell that passes through a 0.1 ?m membrane filter (iii) to screen
biosynthesis gene cluster  for new
complete multi-modular enzymes from PKS and NRPS families, domain
classification exploring their diversity and Phylogeny.