Production of FK520 by Streptomyces tubercidicus

Abstract

The discovery of immunosuppressant compounds created the conditions for the successful transplantations. Effective immunosuppressant compounds were isolated from cultures of different microorganisms, among others macrolide type immunosuppressants, FK506 and FK520, were isolated from the fermentation broths of Streptomyces species. In this study a screening program was carried out to isolate microorganisms, which produce macrolide type immunosuppressant compounds. More than 40,000 actinomycete strains were investigated in the screening program comprising chemical, microbiological and PCR methods for the investigation of the cultures. Actinomycete strains with FK520 biosynthesizing ability were isolated in the program, which were identified as isolates of the Streptomyces tubercidicus species according to the taxonomical investigations. A part of the 31-O-demethyl-FK520 methyltransferase gene of the isolated S. tubercidicus was sequenced and it showed 88% homology to that of Streptomyces hygroscopicus. Till now strains of the Streptomyces hygroscopicus species were known to produce FK520 and this study proved that strains of other Streptomyces species have FK520 biosynthetic ability.

Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules against Multiresistant Pathogens

“…Streptomyces tubercidicus is known to produce tubercidin, a potent substance that can inhibit several metabolic processes, including pathogens, such as Trypanosoma cruzi, viruses, fungi, and present a cytotoxic activity. However, few studies have been done on the isolation of S. tubercidicus and only four have been published in the production of bioactive substances [92,93]. Ratti [94] endophytically isolated the strain of Streptomyces tubercidicus (RND-C) from Solanum lycocarpum Saint Hill, a medicinal plant typically found in the Brazilian tropical savannah, known for its anti-inflammatory properties.…”

Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis, tumour rapalog resistance and probiotics

“…Streptomyces hygroscopicus can also produce the well-known FK520 immunosuppressant. Streptomyces tubercidicus produces tacrolimus (FK506) and FK520 immunosuppressants (Konya et al, 2008). In addition to the therapeutically relevant products (rapamycin, tacrolimus and FK520) (Tamaki et al, 2008), Streptomycetes produce some other immunosuppressants whose clinical applications are needed to be determined.…”

“…Streptomyces bacteria are generally in soil (Vezina et al, 1975;Konya et al, 2008;Seipke et al, 2012) though their contacts with mucosal surfaces, including the digestive and respiratory tracts, and skin seems to have been inevitable far back in the past during evolution and even in the current industrialized lifestyle (Supporting Information File 1, b). In fact, the production of secondary metabolites must be as the result of Streptomyces' interaction with other cells.…”