UNLOCKING “SILENT” GENES VIA COMBINE CULTURE–AN ALTERNATIVE GATEWAY TO NATURAL PRODUCTS DISCOVERY

Streptomyces sp. has been known to produce antibiotics and other bioactive natural products. However, the production of these secondary metabolites depends on the culture conditions, where in most cases the secondary-metabolite genes are not expressed in fermentation culture. Recently, a novel fermentation method known as combined-culture has been introduced to unlock these “silent” genes, hence induces the production of cryptic metabolites. We report herein, our preliminary work on combined-culture using two soil-borne bacterial strains; Streptomyces and Tsukamurella. From the results, it is shown that the presence of Tsukamurella, a mycolic acid-containing bacterium induces the production of new metabolites in Streptomyces. Moreover, the production of compounds associated with Streptomyces was enhanced via combination-culture as compared to culture of Streptomyces strain alone. These findings may promote the feasibility of combined-culture in unlocking the “silent” genes of microorganisms which could lead to the discovery of novel metabolites.

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Phytoplankton of the Curonian Lagoon as a New Interesting Source for Bioactive Natural Products. Special Impact on Cyanobacterial Metabolites

Biomolecules ◽

10.3390/biom11081139 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1139

Author(s):

Donata Overlingė ◽

Anna Toruńska-Sitarz ◽

Marta Cegłowska ◽

Agata Błaszczyk ◽

Karolina Szubert ◽

...

Keyword(s):

Natural Products ◽

Serine Proteases ◽

Ex Situ ◽

Breast Adenocarcinoma ◽

Curonian Lagoon ◽

Bacterial Strains ◽

Biotechnological Potential ◽

Bioactive Natural Products ◽

Field Samples ◽

Sample Component

The bioprospecting of marine and brackish water systems has increased during the last decades. In this respect, microalgae, including cyanobacteria, and their metabolites are one of the most widely explored resources. Most of the bioactive compounds are isolated from ex situ cultures of microorganisms; however, analysis of field samples could also supply valuable information about the metabolic and biotechnological potential of microalgae communities. In this work, the activity of phytoplankton samples from the Curonian Lagoon was studied. The samples were active against antibiotic resistant clinical and environmental bacterial strains as well as against serine proteases and T47D human breast adenocarcinoma cells. No significant effect was found on Daphnia magna. In addition, using LC-MS/MS, we documented the diversity of metabolites present in field samples. A list of 117 detected cyanopeptides was presented. Cyanopeptolins constituted the largest class of cyanopeptides. As complex bloom samples were analyzed, no link between the observed activity and a specific sample component can be established. However, the results of the study showed a biotechnological potential of natural products from the Curonian Lagoon.

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Mycolic Acid-Containing Bacteria Induce Natural-Product Biosynthesis inStreptomycesSpecies

Applied and Environmental Microbiology ◽

10.1128/aem.01337-10 ◽

2010 ◽

Vol 77 (2) ◽

pp. 400-406 ◽

Cited By ~ 151

Author(s):

Hiroyasu Onaka ◽

Yukiko Mori ◽

Yasuhiro Igarashi ◽

Tamotsu Furumai

Keyword(s):

Natural Products ◽

Natural Product ◽

Rhodococcus Erythropolis ◽

Direct Interaction ◽

Culture Method ◽

Mycolic Acid ◽

Culture Conditions ◽

Natural Product Synthesis ◽

Outer Cell ◽

Natural Product Biosynthesis

ABSTRACTNatural products produced by microorganisms are important starting compounds for drug discovery. Secondary metabolites, including antibiotics, have been isolated from differentStreptomycesspecies. The production of these metabolites depends on the culture conditions. Therefore, the development of a new culture method can facilitate the discovery of new natural products. Here, we show that mycolic acid-containing bacteria can influence the biosynthesis of cryptic natural products inStreptomycesspecies. The production of red pigment byStreptomyces lividansTK23 was induced by coculture withTsukamurella pulmonisTP-B0596, which is a mycolic acid-containing bacterium. Only living cells induced this pigment production, which was not mediated by any substances.T.pulmoniscould induce natural-product synthesis in otherStreptomycesstrains too: it altered natural-product biosynthesis in 88.4% of theStreptomycesstrains isolated from soil. The other mycolic acid-containing bacteria,Rhodococcus erythropolisandCorynebacterium glutamicum, altered biosynthesis in 87.5 and 90.2% of theStreptomycesstrains, respectively. The coculture broth ofT.pulmonisandStreptomyces endusS-522 contained a novel antibiotic, which we named alchivemycin A. We concluded that the mycolic acid localized in the outer cell layer of the inducer bacterium influences secondary metabolism inStreptomyces, and this activity is a result of the direct interaction between the mycolic acid-containing bacteria andStreptomyces. We used these results to develop a new coculture method, called the combined-culture method, which facilitates the screening of natural products.

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