The antimicrobial activity of two cyanobacterial exometabolites, norharmane (9H-pyrido(3,4-b)indole) and 4,4'-dihydroxybiphenyl, was determined in suspension assays. Good anticyanobacterial activities (concentrations of 8-80 microg ml(-1)) and moderate antibacterial (16-160 microg ml(-1)) and antifungal (32-40 microg ml(-1)) activities were found for both compounds. The natural function as allelopathic chemicals and a possible applicability as antifouling agents or leads for the development of new antifouling chemicals are discussed.

Culture medium extracts obtained from 115 culture media of 35 different microalgae species were screened for the presence of algicidal compounds, in particular for compounds which are cytotoxic to Arthrospira (Spirulina) laxissima. In agar plate diffusion tests and in a test system combining thin layer chromatography (TLC) with the use of an aqueous suspension of living A. laxissima cells as spray reagent, 14 microalgae species were found with cytotoxic activity of different intensity to A. laxissima. In a so-called TLC plate diffusion test, using A. laxissima and other microalgae as test organisms, the culture medium extracts of Nodularia harveyana and Nostoc insulare possessed the highest strength and range of algicidal activity. The algicidal compound in the culture medium extracts of Nodularia harveyana was shown to be norharmane (9H-pyrido(3,4-b)indole), a known indole alkaloid. The main algicidal compound in culture medium extracts of Nostoc insulare was identified as 4,4 -dihydroxybiphenyl. The possible applicability of both compounds as therapeutics or as useful agents for removing cyanobacterial water blooms or for developing new antifouling systems is discussed.

A screening of microalgae strains is described, with the objective to discover more species besides the known cyanobacterium Nodularia harveyana which excrete the manifold biologically active and co-mutagenic indole alkaloid norharmane (9H-pyrido(3,4-b)indole) into their environment. Seven more cyanobacterial species, Anabaena cylindrica, Anabaena inaequalis, Anabaenopsis siamensis, Chroococcus minutus, Nostoc carneum, Nostoc commune and Phormidium foveolarum, were newly discovered. The norharmane concentrations detected for cyanobacterial culture media varied in a species-dependent manner from less than 1 up to 525 microg l(-1). The risk for humans and livestock, resulting from the natural appearance of norharmane as an extracellular metabolite of various cyanobacteria, is discussed.

Changes in the content of exometabolites excreted by the cyanobacterium Nostoc insulare during batch cultivation were determined. During linear growth, only the non-toxic compound N,N′-(4,5-dimethyl-1,2-phenylene) bis-acetamide was detectable in appreciable quantities in the medium, whereas during stationary growth the antimicrobial and cytotoxic exometabolites 4,4′-dihydroxybiphenyl and 9H-pyrido(3,4-b)indole (norharmane) were also present to an increasing degree. Hence it is proposed that biosynthesis of N,N′-(4,5-dimethyl-1,2-phenylene)bisacetamide in N. insulare is associated with cell proliferation and primary metabolism of this organism. 4,4′-Dihydroxybiphenyl and norharmane, however, are proposed to be products of secondary metabolism that are excreted by N. insulare primarily under nutrient-restricted conditions and under increased pressure of competition with other organisms.Key words antimicrobial activity . 4,4′-dihydroxybiphenyl . N,N′-(4,5-dimethyl-1,2-phenylene)bis-acetamide . fermenter batch cultivation . microalgal culture medium extracts . norharmane (9H-pyrido(3,4-b)indole)

The isolation, identification and quantification of exometabolites from culture media of the cyanobacterium Nostoc insulare are described. Besides the known exometabolite 4,4′-dihydroxybiphenyl (I), two more compounds, the β-carboline 9H-pyrido(3,4-b) indole (norharmane, II) and N,N′-(4,5-dimethyl-1,2-phenylene)bis-acetamide (III), were discovered. Concentrations of all three compounds in media and biomass of five 250 L cultures of N. insulare were determined. Culture medium values for I ranged between 200 and 1,250 μg L −1 (1.1-6.7 μmol L −1 ), for III between 115 and 390 μg L −1 (0.5-1.8 μmol L −1 ), whereas concentrations of II were conspicuously lower (2-16 μg L −1 or 0.014 -0.094 μmol L −1 ). Amounts of III per volume of culture medium were about tenfold higher than in the biomass contained in an equal culture volume. This difference is an indication for an active excretion of III. Amounts of I and II in biomass and media were of no significant difference. In the neutral red uptake assay, I and II were found to be toxic against eukaryotic cells as follows: I was of considerable cytotoxicity in concentrations from 1,000 to 10 mg L −1 and of lower cytotoxicity (causing a 27 % decrease of cell viability) in a concentration of 1,000 μg L −1 , whereas II was merely of considerable cytotoxicity in concentrations from 1,000 to 100 mg L −1 . Because of the cytotoxicity of I and because of the many known pharmacological effects of II there is a possibility that a certain amount of risk to humans and livestock comes from cultures or even from biomassfree culture media of N. insulare. The natural function of the examined exometabolites is discussed.