Modeling improved production of the chemotherapeutic polypeptide actinomycin D by a novel Streptomyces sp. strain from a Saharan soil

Ibtissem Djinni; Andrea Defant; Warda Djoudi; Faouzia Chaabane Chaouch; Samiha Souagui; Mouloud Kecha; Ines Mancini

doi:10.1016/j.heliyon.2019.e01695

Modeling improved production of the chemotherapeutic polypeptide actinomycin D by a novel Streptomyces sp. strain from a Saharan soil

Heliyon. 2019 May 27;5(5):e01695. doi: 10.1016/j.heliyon.2019.e01695. eCollection 2019 May.

Authors

Ibtissem Djinni^{1

2}, Andrea Defant², Warda Djoudi¹, Faouzia Chaabane Chaouch³, Samiha Souagui², Mouloud Kecha¹, Ines Mancini²

Affiliations

¹ Laboratoire de Microbiologie Appliquée, Faculté des Sciences de la Nature et de la Vie, Département de Microbiologie, Université de Bejaia, 06000, Algeria.
² Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, via Sommarive 14, Povo, I-38123, Trento, Italy.
³ Laboratoire de Biologie des Systèmes Microbiens (LBSM), Ecole Normale Supérieure de Kouba, Alger, Algeria.

Abstract

The novel bioactive actinobacterial strain GSBNT10 obtained from a Saharan soil, was taxonomically characterized using a polyphasic approach. 16S rRNA gene sequence analysis supported the classification of the isolate within the genus Streptomyces indicating it as a novel species. The major metabolite responsible of the bioactivity was purified and structurally characterized as actinomycin D (act-D) by mass spectrometric and nuclear magnetic resonance analyses Plackett-Burman design (PBD) and response surface methodology (RSM) were applied in order to optimize the medium formulation for the production of this bioactive metabolite. By PBD experiments, NaNO₃, K₂HPO₄ and initial pH value were selected as significant variables affecting the metabolite production. Central Composite Design (CCD) showed that adjustment of the fermentative medium at pH 8.25, K₂HPO₄ at 0.2 gL^-1 and NaNO₃ at 3.76 gL^-1 were the values suiting the production of act-D. Moreover, the results obtained by the statistical approach were confirmed by act-D detection using the HPLC equipped with a diode array detector and coupled online with electrospray-mass spectrometry (ESIMS) technique. act-D production was highly stimulated, obtaining a good yield (656.46 mgL^-1) which corresponds to a 58.56% increase compared with the non-optimized conditions and data from LC-ESIMS technique efficiently confirmed the forecast from RSM.

Keywords: Actinomycin D; Central composite design; Electrospray mass spectrometry; Microbiology; Optimization; Plackett-Burman design; Saharan saline soil; Streptomyces sp..