Emerging Trends in Discovery of Novel Bioactive Compounds of Microbial Origin

called bioactive The newly discovered antibiotics include monobactum, compactin, thienamycin, avermectin, tunicamycin, bialaphos, staurosporin and FK-506. Similarly, more than 100 bioactive compounds such as avermectin, rokitamycin, nanaomycin, tilmicosin etc., are also discovered in past 19 years. New trends are being developed in the field of finding new antibiotics and bioactive compounds. Some of the current trends are discussed in this review article. The study of these new trends and modern methodology will open new doors in the discovery of new microbial bioactive metabolites [1,2] (Figure 1). ABSTRACT Advance studies interpret the values of microorganisms in the discovery of bioactive metabolites which eventually act as drugs to treat different infections, immune related diseases, and cancer. Bioactive compounds are actively conducive in the field of medicine and agriculture. Different bioactive metabolites have also been discovered from marine microorganisms which are useful in versatile biological activities acting as antitumor, antimicrobial, and anti-inflammatory agents. So, scientists, ecologists and chemists are in creasing their attention to discover the new methods and techniques to extract advance type of bioactive compounds from microorganisms. The review described the main factors which contribute to the discovery of emerging trends for new bioactive metabolites disclosure. These include the assessment of biological activities of compounds (as effec-tor of regulatory factors, lipid metabolism modulators, inhibitor of protein phosphorylation, agrochemicals, and anticancer compounds), discovery of new sources of microbes for active metabolites production, manipulation of genes in biotechnology screening systems and chemical modification. The incorporation of new methods for production of marine microbial metabolites are also given in which products from genomics, metag-enomics, screening system, synthetic biology and combinatorial biosynthesis are includ-ed.


Current Trends in the Studies of Microbial Bioactive Metabolites
New research in the discovery of bioactive metabolites produced from microorganisms has been continued because of their effective chemotherapeutic and long-lasting activities. There

Evolution of Biological Activities
The most significant change is the increased number of active compounds of non-antibiotic nature. According to a report of a database for bioactive microbial metabolites, the total number of reported bioactive compounds was 9046 until 1990. Of these 9046 active compounds, actinomycetes products were the sources for 67% of bioactive microbial metabolites. Before 1965 the research targets were antibiotics but after it the research work was shifted from the discovery of antibiotics to bioactive compounds. Until 1990 the percentage of discovered non-antibiotic bioactive compounds was 53%. But in recent 5 years most of the bioactive compounds have been discovered and are being utilized in various fields. These bioactive compounds include immune-modulators, enzyme inhibitors, and effectors of neurotransmission, receptor binding antagonists and many others. Ergot alkaloids were first bioactive microbial metabolites of non-antibiotic nature which were used in the field of clinical medicine. The second oldest type of microbial metabolites was Gibberellin. These Gibberellins also have non-antibiotic nature.
With the passage of time, it is also discovered that the activities of antibiotics are also changed. Such as the previously known target of antibiotics was only bacteria but now it targets other microorganisms also such as viruses, fungi, and protozoa.
Antibiotics can also target certain invertebrates such as insects,

Mechanism of Action of Bioactive Compounds
Insecticidal Activity: This antiseptic activity of the bioactive compounds was firstly discovered by Hamill from B. bassiana against salina, which was considered to be a model creature for study of pest control. Biologically active chemicals may not be used directly as an insecticide instead of insect repellent, for example entomopathogenic fungi can spread to bodies of insects and spread widely through insect movements. The entomo-pathogenic fungi can produce effective pest control even with the use of a small amount of entomopathogenic fungus particles. Careful examination of the production of bio-active compounds should be made sure that they will not rise above the limits. activities. According to a study some bioactive compounds are most effective inhibitors of cyclic hexadepsi-peptides that inhibit enzyme HIV-1 integrase. But enniatin's have a relatively weaker function despite having the same structure, which means that activity of bioactive compounds is due to a major primary difference,

N-methylation. Viral infection can lead to deadly diseases
and epidemics and anti-viral activity of the biologically active compounds must be studied for effective clinical applications and sensitive viruses such as HBV etc.

Recent Discovery of Bioactive Compounds from Microbial Sources Via Screening Programs
A number of secondary metabolites or bioactive compounds has been isolated from microorganisms and tested to check their effects. Some more common isolated bioactive compounds are discussed below:

Discovery of Compounds Effective for Internal Regulatory Factors
Erythromycin, an antibiotic isolated from Saccharopolyspora   inhibitor is effect to cure such diseases [3][4][5].

Inhibitory Compounds Against Protein Phosphorylation
Phosphorylation of protein, carried out by protein kinases and phosphatases, impart a serious effect on normal functioning of organs sometimes. Some processes like cell growth, its motility and differentiation, metabolism and neurological functions may be affected by protein phosphorylation. As protein kinase in responsible for this mainly, so it is the main target for inhibitors, to prevent coagulation, asthma and hypertension etc. Several inhibitors against protein phosphorylation have been isolated from microorganisms like staurosporin inhibitor isolated from Saccharothrix sp. by screening methods. Staurosporine provides a number of pharmacological activities as it is a potent, competitive inhibitor against kinase C. however, it shows nonspecific against kinase A and B. it has also been observed that staurosporin works in relaxing rabbit aortic strips (agonists contract them).
Another inhibitor against tyrosine kinase which is also isolated from streptomyces sp. is herbimycin (A, B and C). It has been found that herbimycin A works effectively in conversion of transformed cells caused by kinases to normal state. Erbstatin is another important product which acts as inhibitor against tyrosine kinase.
As protein phosphorylation may also occur due to phosphatases.

Two important inhibitors of phosphatases are Okadaic acid and
tautomycin. Both are significant in studying protein phosphorylation mechanism and its role in signal transduction, carcinogenesis as well as in drug development.

Bioactive Compounds Against Cancer
In order to control bacterial, fungal and viral infections, discovery of excellent chemotherapeutic agents is still a need. Now a days, cancer is going out of our control due to lack of proper therapeutic agents. However, efforts are continuous for discovery

Production of Bioactive Compounds by using Novel Sources of Microbes
The major and most significant sources for the production This strategy is enhancing as it provides novel metabolites along with the structures of metabolites.

Recombinant DNA Technology
Various applications of this approach for the study of bioactive compounds can be categorized in two groups. In the first category, the metabolites are engineered genetically for following purposes.

Production of Marine Microbial Natural Products
There is a significant need of innovative antibiotics to cope with various diseases along with resistant disease-causing microorganisms that have become a major threat for the health of community. In order to discover various diseases plants, animals as well as certain strains of microorganisms have been used.
However, due to recent increase in the diseases there is a critical need to produce novel antibiotics. Current strategies involve the use of marine samples to produce innovative bioactive compounds.
Some of the most significant and widely used approaches for the discovery or production of bioactive compounds are discussed here:

Production of Bioactive Compounds by Meta-Genomics
Meta-genomics is the widely used and significant approach that enables the researchers to access the genetic material of microbes directly, without cultured them in laboratory through the isolation of environmental DNA of microbes. By using this approach, various bioactive compounds have been discovered along with their distinctive configurations that include violacein, terragins as well as turbomycins. The shortcomings or disadvantages of this approach involve incompetence of effective achievement of integral portion of gene as well as incompatibility of certain expressive components in their respective host.

Marine Microbial Bioactive Compounds Through Combinatorial Biosynthesis
The production of derivatives through chemical synthesis The combinatorial biosynthesis can also generate unnatural derivatives of salinosporamide including antiprotealide by certain modifications in the proteasome inhibitors. There is also a limitation in the use of combinatorial biosynthesis with its importance that the derived compounds have less productivity than parent compounds.
And there is no collection of modified compounds which may be improved in coming days.

Different Microbial Bioactive Compounds Through Synthetic Biology
There are large number of very effective technologies have developed which elucidate the structure and activity of many natural products. The diversity in structure can give a pool of drugs but due to their high cost of production, they are not reachable to ordinary people. The discovery of synthetic biology has led to the production of compounds. It can assemble in the host microbes the

Production of Bioactive Compounds by Pathway Engineering
For increased production of biologics, the technology of pathway engineering can also be applied by using the process of

Production of Bioactive Compounds by Precursor Supply Engineering
Precursor molecule supply is the increase in the accessibility of the metabolites that are necessary or important for the synthesis of biologics. These primary metabolites are obtained from primary metabolism and have an important and effective role in the production of microbial products. By the manipulation of enzymes coli, the production of yersiniabactin was enhanced up to 175mg/L by introducing the cysteine molecules to the E. coli culture. This technology is also applied for enhanced production of natural products that is achieved by reducing by products formation that are not required. In E. coli, for example, acetate production i.e., a by-product is the primary hindrance in recombinant protein production. This by-product is formed during the process of aerobic But this approach is not sufficient for the discovery of new biologics, specifically marine plants that are endophytes. Due to the mistreatment of antibiotics, many microbial strains have developed the resistance against many drugs. That is why, the production of novel drugs is highly demanding. There is also needed to do