Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus

Abstract

Modern antifouling coatings use heavy metals and toxic organic molecules to prevent biofouling, the undesirable growth of marine organisms on man-made substrata. In an ongoing survey of deep-sea microorganisms aimed at finding low toxic antifouling metabolites, an actinomycete bacterium was isolated from the Pacific sediment at the depth of about 5000 m. The bacterium was closely related to Streptomyces fungicidicus (99% similarity) according to 16S ribosomal RNA sequence information. The spent culture medium of this bacterium inhibited barnacle larval attachment. Bioassay-guided fractionation was employed to isolate antifouling compounds. The ethyl acetate extract was fractionated by using an open silica gel column. Active fractions were further purified on a HPLC C 18 column., and cyclo-(L-Leu-L-Val) were isolated for the first time from a deep sea bacterium, and the structures of the compounds were elucidated by nuclear magnetic resonance spectroscopy and mass spectrometry. The pure diketopiperazines were tested for antilarval activity using the barnacle Balanus amphitrite. Effective concentrations that inhibited 50% larval attachment (EC 50 ) after 24 h ranged from 0.10 -0.27 mM. The data suggest that diketopiperazines and other compounds from deep-sea bacteria may be used as novel antifoulants.

Inhibition of biofilm in Bacillus amyloliquefaciens Q-426 by diketopiperazines

“…The bacterial capsular polysaccharide was found to inhibit many bacteria biofilm formation (Goncalves et al 2014), and a set of proteases immobilized on chitosan showed anti-biofilm activities on several pathogenic bacteria (Elchinger et al 2014). Diketopiperazines (DKPs), otherwise referred as cyclic dipeptides, have attracted the attention of microbial researchers for their biological activities including antibacterial (Prasad 1995;Qi et al 2009;De Carvalho and Abraham 2012;ElGendy and Rateb 2015), antifungal (Byun et al 2003), antifouling (Li et al 2006), antilarval (Qi et al 2009), and antitumor (Du et al 2010;Wang et al 2015) activities. DKPs have been isolated from various microorganisms, such as from fungi like Fusarium oxysporum (Trigos et al 1995), Porphyra yezoensis (Byun et al 2003), and Penicillium sp.…”

“…(Kumar et al 2012;Wang et al 2010a); and from actinomycetes like Streptomyces spp. (Cho et al 2012;Li et al 2006).…”

A new minor diketopiperazine from the sponge-derived fungus Simplicillium sp. YZ-11

“…In recent years, the antifouling activities of the diketopiperazines had been studied. Li et al (2006) isolated five diketopiperazines from a deepsea bacterium, Streptomyces fungicidicus. The antifouling activity against the larval of the barnacle Balanus amphitrite of those diketopiperazines indicated potential application as novel antifoulants.…”

“…Cyclo-(2-hydroxy-Pro-Gly) (1) is structurally similar to cyclo-(Pro-Gly), and possesses a 2,5-diketopiperazine unit. In marine environment, diketopiperazines as the smallest cyclic peptides are widely produced by marine microorganisms, especially marine bacteria (Jayatilake et al 1996;Li et al 2006;Yu et al, 2014). They are extensively obtained by extraction from natural sources, but may be easily synthesised.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Overall, 2,5-diketopiperazine derivatives emerged in the last decade as very attractive molecules in drug discovery [204][205][206][207][208][209][210]. Indeed, these derivatives usually exhibit various biological properties [211], including antitumor [212,213] antiviral [214], antifungal [215,216] antibacterial [217,218] or antifouling activities [219]. Interestingly, their role in the bitter taste of coffee, beer, cacao and chocolate has been highlighted [220].…”