Optimization of Pre-Inoculum, Fermentation Process Parameters and Precursor Supplementation Conditions to Enhance Apigenin Production by a Recombinant Streptomyces albus Strain

Abstract

Streptomyces albus J1074-pAPI (Streptomyces albus-pAPI) is a recombinant strain constructed to biotechnologically produce apigenin, a flavonoid with interesting bioactive features that up to now has been manufactured by extraction from plants with long and not environmentally friendly procedures. So far, in literature, only a maximum apigenin concentration of 80.0 µg·L−1 has been obtained in shake flasks. In this paper, three integrated fermentation strategies were exploited to enhance the apigenin production by Streptomyces albus J1074-pAPI, combining specific approaches for pre-inoculum conditions, optimization of fermentation process parameters and supplementation of precursors. Using a pre-inoculum of mycelium, the apigenin concentration increased of 1.8-fold in shake flask physiological studies. In 2L batch fermentation, the aeration and stirring conditions were optimized and integrated with the new inoculum approach and the apigenin production reached 184.8 ± 4.0 µg·L−1, with a productivity of 2.6 ± 0.1 μg·L−1·h−1. The supplementation of 1.5 mM L-tyrosine in batch fermentations allowed to obtain an apigenin production of 343.3 ± 3.0 µg·L−1 in only 48 h, with an increased productivity of 7.1 ± 0.1 μg·L−1·h−1. This work demonstrates that the optimization of fermentation process conditions is a crucial requirement to increase the apigenin concentration and productivity by up to 4.3- and 10.7-fold.

Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation

“…The Streptomyces genus is distinguished for its complicated life cycle, which includes morphological and developmental stages that influence metabolite formation. The optimization of Streptomyces albus fermentation conditions for the manufacturing of specific bioactive molecules, as well as the scaling-up of the biotechnological process in a bioreactor with controlled parameters, are also areas that have yet to be explored 61 . In order to maximize productivity and growth yields, incubation temperature, pH, medium composition, oxygen levels, aeration, and agitation should all be optimized in the design of a biotechnological manufacturing process of industrially interesting chemicals 62,63 .…”

Chromium Flavonoid Complexation in an Antioxidant Capacity Role

“…They are involved in the control of respiration, photosynthesis, morphogenesis, and sex determination, as well as defense against infections [8][9][10]. Despite the fact that they are found in the plant kingdom and are isolated through extraction techniques, there has been much research work done to increase their production using bacterial species, i.e., Streptomyces albus, targeting apigenin, kaempferol, luteolin, eriodictyol, and quercetin [11][12][13][14].…”

Actividad antimicrobiana de Streptomyces sp. Y15 contra bacterias patógenas y evaluación de medios de cultivo para la producción de antibióticos

“…The complex life cycle of streptomycetes, their high physiological versatility, and their ability to produce a large variety of secondary metabolites are all reflected in streptomycetes' genome size. The production of biologically active secondary metabolites is species-specific, and their production depends on the culture conditions and on the nutritional factors in the fermentation medium (de Lima Procópio et al, 2012;Barbuto Ferraiuolo et al, 2021). For instance, antibiotic production by Streptomyces sp.…”