Marine actinobacteria:

an important source of bioactive

natural products

Presented by

Akram Najafi

Marine actinobacteria

• Actinobacteria are a group of Gram positive bacteria.

• They can be terrestrial (soil) or aquatic (freshwaters).

• Form of a very few colonies

• Cannot grow under laboratory conditions

• They can be isolated from:

- Seashores

- Coastal waters

- Bottom sediments

- Fishes

- Molluscs

- Sponges

- Seaweeds

- Mangroves

Problem!

• In spite of the improvements being made in the cultural

methods for the isolation of rare marine actinobacteria,

many of these organisms still remain unculturable and

have to be detected by using molecular techniques.

• Metagenomic methods, therefore will be useful for

characterizing microbes that cannot be cultivated and

can also be used to isolate their genes.

The most important roles:

• Marine actinobacteria are the most economically and biotech-nologically priceless prokaryotes.

• Actinobacteria, have potential to :

- Produce novel, bioactive natural products

- Produce pharmaceutically active secondary metabolites.

- Produce 70% of the naturally derived compounds that are currently inclinical use.

• The important role of marine actinobacteria:

- Antimicrobial

- Anticancer

- Antithrombotics

- Antiviral

- Antifungal

- Insecticidal

- Enzyme inhibitory activities

- Growth promoting substances

The most important genera:• The major producers of commercially important bioactive natural

products:

• Streptomyces

• Actinomadura

• Actinoplanes

• Amycolatopsis

• Marinispora

• Micromonospora

• Nocardiopsis

• Saccharopolyspora

• Salinispora

• Verrucosispora

• In fact, the genus Streptomyces alone accounts for a remarkable80% of the actinobacterial natural products reported to date.

• Sediments and sponges are the most studied marine

samples for actinomycetes isolation.

• The production of most antibiotics is species specific,

and these secondary metabolites are important for

Streptomyces species in order to compete with other

microorganisms that come in contact, even within the

same genre.

The history of antibiotics derived

from Streptomyces began with the

discovery of streptothricin in 1942,

and with the discovery of

streptomycin in 1944.

Today, 80% of the antibiotics

are sourced from the genus

Streptomyces, actinomycetes being

the most important.

• Indeed, each strain of actinobacteria is likely to have the genetic

potential for the production of 10–20 secondary metabolites

• About 23,000 antibiotics have been discovered from

microorganisms.

• It has been estimated that approximately 10,000 of them have

been isolated from actinobacteria.

Actinomycete-derived antibiotics

• The most important antibiotics in medicine:

- Aminoglycosides

- Anthracyclines

- Chloramphenicol

- Macrolide

- Tetracyclines

Different types of antibiotic groups

• Polyketides

• Peptides

• Quinones

• Macrolides

• Terpenes

• Alkaloids

• Indole compounds

• Pyrroloiminoquinone

• Butenolides

• Esters

Benzoxazole

Piericidins

Methylpyridine

Trioxacarcins

Marinopyrroles

Manumycin derivatives

Triazolopyrimidine

Macrocyclic lactam

Sisomicin

Novel secondary metabolites produced by

marine actinobacteria

Antibacteria Activity

Abyssomicin C:

• A novel polycyclic polyketide antibiotic.

• Inhibitor of para-aminobenzoicacid biosynthesis = inhibits the

folic acid biosynthesis = synthetic sulfa drugs.

• Abyssomicin C possesses potent activity against Gram positive

bacteria.

• Is an unique farnesylated dibenzodiazepinone.

• It possesses antibacterial, antiinflammatory, antitumor activity.

• It has a broad spectrum of in vitro cytotoxicity

• In vivo activity against glioma, breast and prostate cancer in

mouse models.

Diazepinomicin:

• It showed inhibitory activity against Gram positive bacteria.

• Inhibitory activity against the tumor cell lines gastric

adenocarcinoma (AGS), hepatocellular carcinoma (Hep G2)

and breast carcinoma cells (MCF7) and enzyme phospho

diesterase.

Caboxamycin:

Anticancer

• An anticancer and antimalarial drug.

• A novel rare bicyclic beta-lactonegamma-lactam.

• An orally active proteasome inhibitor that induces apoptosis inmultiple myeloma cells.

• It is interesting to note that chloroquine resistant strains are stillsensitive to Salinosporamide A.

• Targeting the proteasome system has a huge therapeuticimplication as it can restrain growth and survival of most celltypes.

Salinosporamide A:

Cytotoxic activity

Marinomycins:• Significant antimicrobial activities against:

- Drug resistant bacterial pathogens

- Selective cancer cell cytotoxicities against six of the eight

melanoma cell lines in the National Cancer Institute’s 60

cell line panel.

Antitumor activity

• Recent investigations using enrichment techniques, new

selection methods and media have led to the isolation of novel

actinomycetes from sediment samples.

• Improved recovery yields of marine actinomycetes from

sponges using nutrient supplements and enzymes have

been reported

• These recent successes are the first step in the right direction.

Further development work in improving isolation strategies

in the recovery of marine actinomycetes is of utmost

importance for ensuring success in this area.

Conclusion

• It seems likely that two major parallel approaches will bedeveloped for drug discovery from marine acti-nobacteria.

• One will be based on establishment of new and furtherdevelopment of existing isolation and cultivation techniques,to increase the diversity of cultivable isolates, shorten thetime of cultivation to achieve appreciable cell mass for higheryields and production of secondary metabolites.

• As the actinobacteria are very diverse and each species mighthave special requirements not only for growth, but also forthe production of secondary metabolites, this approach willrequire considerable novel and innovative efforts.

• Its major advantage is that, if successful, it will result in theproduction of a compound whose structure, novelty andbiological activity can be assessed straight away.

Thank you for your

attention