Research Article: Bioactive metabolites produced by Streptomyces Cheonanensis VUK-A from Coringa mangrove sediments: isolation, structure elucidation and bioactivity

Date Published: February 13, 2016

Publisher: Springer Berlin Heidelberg

Author(s): Ushakiranmayi Mangamuri, Vijayalakshmi Muvva, Sudhakar Poda, Krishna Naragani, Rajesh Kumar Munaganti, Bhujangarao Chitturi, Venkateswarlu Yenamandra.


The strain VUK-A was isolated from a sediment sample of the Coringa mangrove ecosystem was identified as Streptomyces cheonanensis based on morphological, physiological, biochemical and molecular properties. Chemical investigation of the secondary metabolites of the strain Streptomyces cheonanensis VUK-A has led to the segregation of two bioactive compounds, namely 2-Methyl butyl propyl phthalate (1) and Diethyl phthalate (2) using column chromatography. The chemical structure of the active compounds was established on the basis of spectroscopic analysis, including 1H NMR and 13C NMR spectroscopies, FTIR and EIMS. The antimicrobial activity of the bioactive compounds produced by the strain was tested against a wide variety of bacteria and fungi and expressed in terms of minimum inhibitory concentration. The compounds (1&2) were active against all the bacteria tested, and the best activity of compound 1 was recorded against Proteus vulgaris (4 µg/ml). Compounds (1&2) were active against dermatophytes and fungi but compound 1 displayed high antifungal activity against Candida albicans (8 µg/ml) and Fusarium solani (16 µg/ml) compared to standard antifungal agents. The cytotoxicity of the bioactive compound 1 was tested against MDA-MB-231, OAW-42, HeLa, and MCF-7 cell lines. The highest activity of 100 µM by compound 1 was recorded against HeLa cancer cell lines. In fact, this is the first report of 2-Methyl butyl propyl phthalate from the genus Streptomyces.

Partial Text

Microbes are the factors for a multitude of human diseases, but also equally owe a great extent to human medicine, disease treatment and control. This is due to the fact that marine microbes yield natural products and their synthetic analogs represent a large dimension of the drugs with clinical application and treatment for infectious disease as antibiotics (Jerry Reen et al. 2015). These natural product drugs are often highly potent, active and highly specific to the cellular targets (Koehn and Carter 2005). Introduction of these compounds into clinical practice begins to elevate the antibiotic resistant bacteria with many strains spread across the globe (Woodford et al. 2011; So et al. 2011) due to increased antibiotic usage. The situation is worsened with the promotion of few specific antibiotics in recent years and also decreases of funds for the discovery of the new drugs by the big pharma (So et al. 2011). Most of the recent new drugs derived from the pre-existing scaffolds are active against gram-positive pathogens, but the major threat comes from the gram-negative pathogens where these drugs remain ineffective (Freire-Moran et al. 2011
). This validates that drug resistant pathogens coupled with decline in the development of new chemical entities pull the world back into pre antibiotic era unless the situation is decisively addressed forthwith (Pidot et al. 2014). This situation can be improved by not only in the form of discovering new antibiotics but also isolation and identification of new sources of bioactive compounds. The recorded sources for novel drug leads include actinomycetes predominately the genus Streptomyces (Watve et al. 2001).

During the course of our screening programme for bioactive secondary metabolites from Coringa mangrove ecosystem, Streptomyces cheonanensis VUK-A exhibited significant bioactivity. A novel 2-Methyl butyl propyl phthalate (1) along with a known compound Diethyl phthalate (2), was isolated from the fermentation broth of the strain grown on lactose-peptone broth. Phthalate compounds are petrochemicals used as plasticizers or solvents in a variety of industrial products and also used in food handling and storage while some of them are considered to be ubiquitous pollutants, with slight endocrine disrupting properties (Cespedes et al. 2004). Phthalate derivatives which are biologically active compounds are also effective against demodicidosis and also drug channeling agents (Makhija and Vavia 2003; Marchetti et al. 2002). Many phthalate derivatives have been isolated from plants, terrestrial and marine microorganisms, fungal and bacterial culture broths, especially from the genus Streptomyces (Sastry and Rao 1995; El-Naggar 1997; Chen 2004; Roy et al. 2006). The isolation of compound 2 was previously reported as a natural product from Streptomyces sp.1010, isolated from shallow sea sediment from the region of Livingston Island, Antarctica (Ivanova et al. 2001) and Helicobacter pylori (Keire et al. 2001). It has been reported that complexes derived from diethyl phthalate have antifungal activity (Raman and Parameswari 2007). Many phthalate derivatives such as bis-(2-ethyl hexyl) phthalate, bis-(5-ethyl heptyl) phthalate and dibutyl phthalates were reported from Streptomyces sp.TN 256 strain, Streptomyces bangladeshiensis and Nocardia levis exhibited several antimicrobial activities (Smaoui et al. 2012; Kavitha et al. 2009). However this is the first report of compound 2-Methyl butyl propyl phthalate (1), from the genus Streptomyces, and no information is available on the isolation and characterization of 2-Methyl butyl propyl phthalate from microorganisms, particularly actinomycetes.

The two bioactive compounds (1 & 2) of the present work extracted from the strain VUK-A exhibited significant antimicrobial activity against opportunistic and pathogenic bacteria and fungi. The compound 1 showed potent cytotoxicity against MDA-MB-231, HeLa, MCF-7 and OAW-42 cell lines. There is no information available on the antimicrobial and cytotoxicity of the reported bioactive compound 1 and this is the first report of isolation and characterization of 2-Methyl butyl propyl phthalate from the genus Streptomyces.




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