Effects of addition of elicitors on rimocidin biosynthesis in Streptomyces rimosus M527

Front. Bioeng. Biotechnol.

Ścigaczewska

Bizukojć

2021

Microbial co-cultivation is an approach frequently used for the induction of secondary metabolic pathways and the discovery of novel molecules. The studies of this kind are typically focused on the chemical and ecological aspects of inter-species interactions rather than on the bioprocess characterization. In the present work, the co-cultivation of two textbook producers of secondary metabolites, namely Aspergillus terreus (a filamentous fungus used for the manufacturing of lovastatin, a cholesterol-lowering drug) and Streptomyces rimosus (an actinobacterial producer of an antibiotic oxytetracycline) in a 5.5-L stirred tank bioreactor was investigated in the context of metabolic production, utilization of carbon substrates and dissolved oxygen levels. The cultivation runs differed in terms of the applied co-culture initiation strategy and the composition of growth medium. All the experiments were performed in three bioreactors running in parallel (corresponding to a co-culture and two respective monoculture controls). The analysis based upon mass spectrometry and liquid chromatography revealed a broad spectrum of more than 40 secondary metabolites, including the molecules identified as the oxidized derivatives of rimocidin and milbemycin that were observed solely under the conditions of co-cultivation. S. rimosus showed a tendency to dominate over A. terreus, except for the runs where S. rimosus was inoculated into the already developed bioreactor cultures of A. terreus. Despite being dominated, the less aggressive strain still had an observable influence on the production of secondary metabolites and the utilization of substrates in co-culture. The monitoring of dissolved oxygen levels was evaluated as a fast approach of identifying the dominant microorganism during the co-cultivation process.

Section: Resultsmentioning

confidence: 99%

“Microbial Wars” in a Stirred Tank Bioreactor: Investigating the Co-Cultures of Streptomyces rimosus and Aspergillus terreus, Filamentous Microorganisms Equipped With a Rich Arsenal of Secondary Metabolites

Front. Bioeng. Biotechnol.

Ścigaczewska

Bizukojć

2021

“…Several recent studies focused on the production of oxytetracycline, a broad-spectrum antibiotic, by Streptomyces rimosus [ 8 , 9 , 10 , 11 ]. This species is also known to secrete an antifungal substance rimocidin [ 12 , 13 ] and harbors the genetic basis for the desferrioxamine siderophore biosynthesis [ 14 ]. In a recent study, Kuhl et al [ 15 ] demonstrated that inoculating actinobacteria into the liquid medium containing talc microparticles resulted in morphological and production-related alterations compared to the conventional cultures.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Oxytetracycline Production by Streptomyces rimosus in Submerged Co-Cultures with Streptomyces noursei

Ścigaczewska

2021

Molecules

In the present study, Streptomyces rimosus was confronted with Streptomyces noursei, Penicillium rubens, Aspergillus niger, Chaetomium globosum, or Mucor racemosus in two-species submerged co-cultures in shake flasks with the goal of evaluating the oxytetracycline production and morphological development. The co-culture of S. rimosus with S. noursei exhibited stimulation in oxytetracycline biosynthesis compared with the S. rimosus monoculture, whereas the presence of M. racemosus resulted in a delay in antibiotic production. Different strategies of initiating the “S. rimosus + S. noursei” co-cultures were tested. The improvement in terms of oxytetracycline titers was recorded in the cases where S. noursei was co-inoculated with S. rimosus in the form of spores. As the observed morphological changes were not unique to the co-culture involving S. noursei, there was no evidence that the improvement of oxytetracycline levels could be attributed mainly to morphology-related characteristics.

“…S. rimosus is a producer of oxytetracycline, a popular antibiotic used predominantly for acne treatment (Zouboulis and Piquero-Martin 2003 ). In addition to oxytetracycline, S. rimosus commonly secretes an antifungal substance known as rimocidin (Petković et al 2006 ; Song et al 2020 ; Zhao et al 2019 ). Finally, the third study was designed as the “ Ascomycetes vs. Basidiomycetes ” confrontation between the two evolutionarily distant fungal species.…”

Section: Introductionmentioning

confidence: 99%

Co-cultivation of filamentous microorganisms in the presence of aluminum oxide microparticles

Appl Microbiol Biotechnol

Antecka

2022

In the present work, the approaches of submerged co-cultivation and microparticle-enhanced cultivation (MPEC) were combined and evaluated over the course of three case studies. The filamentous fungus Aspergillus terreus was co-cultivated with Penicillium rubens, Streptomyces rimosus, or Cerrena unicolor in shake flasks with or without the addition of aluminum oxide microparticles. The influence of microparticles on the production of lovastatin, penicillin G, oxytetracycline, and laccase in co-cultures was compared with the effects recorded for the corresponding monocultures. In addition, the quantitative analyses of morphological parameters, sugars consumption, and by-products formation were performed. The study demonstrated that the influence of microparticles on the production of a given molecule in mono- and co-culture may differ considerably, e.g., the biosynthesis of oxytetracycline was shown to be inhibited due to the presence of aluminum oxide in “A. terreus vs. S. rimosus” co-cultivation variants but not in S. rimosus monocultures. The differences were also observed regarding the morphological characteristics, e.g., the microparticles-induced changes of projected area in the co-cultures and the corresponding monocultures were not always comparable. In addition, the study showed the importance of medium composition on the outcomes of MPEC, as exemplified by lovastatin production in A. terreus monocultures. Finally, the co-cultures of A. terreus with a white-rot fungus C. unicolor were described here for the first time. Key points • Aluminum oxide affects secondary metabolites production in submerged co-cultures. • Mono- and co-cultures are differently impacted by the addition of aluminum oxide. • Effect of aluminum oxide on metabolites production depends on medium composition.