TITLE:
Caerulomycin A—An Antifungal Compound Isolated from Marine Actinomycetes
AUTHORS:
Vaibhav Ambavane, Pradipta Tokdar, Rajashri Parab, E. S. Sreekumar, Girish Mahajan, Prabhu Dutt Mishra, Lisette D’Souza, Prafull Ranadive
KEYWORDS:
Caerulomycin A, Antifungal, Non-Polyene, Actinoalloateichus cyanogriseus, Marine Actinomycetes
JOURNAL NAME:
Advances in Microbiology,
Vol.4 No.9,
July
28,
2014
ABSTRACT: Actinomycetes have
been prolific sources of novel secondary metabolites with a range of biological
activities that may ultimately find application as therapeutic compounds. Hence
several drug discovery companies are engaged in isolation of novel bioactive
metabolites from these microbial sources. Antibiotics form the major class of
such bioactive metabolites and have been widely used for treating infectious
diseases. One of the most critical problems in clinical practice is the increase
of prevalence of drug resistant strains, especially azole resistance among
fungi. Due to this, there is a constant need for development of new antifungal
antibiotics having novel scaffolds and/or mechanism of action. In our in-house
screening program in the quest of novel and superior antifungal compounds, an
actinomycetes strain PM0525875 was isolated from a marine invertebrate. The
extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active
peak from the extract obtained by shake flask fermentation was identified by
chromatographic and other analytical techniques during bioactivity guided
isolation. Later the fermentation conditions were optimized in 30 L fermentor
for the production of sufficient amount antifungal compound for complete
structural characterization. Consequently the fermented broth extract was
subjected to bioactivity-guided fractionation, to isolate the active principle
using different preparative chromatographic techniques followed by its
characterization. The active principle was characterized to be Caerulomycin A.
Minimum inhibitory concentration (MIC) of the compound was found in the range
of 0.39 - 1.56 μg/ml against pathogenic fungal test strains. The phylogenetic
analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus.
Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized
medium and fermentation conditions.