Whole-Cells of Yarrowia lipolytica Applied in “One Pot” Indolizine Biosynthesis

• Published in: Catalysts 2020-06, Vol.10 (6), p.629
• Main Authors: Botezatu (Dediu), Andreea Veronica, Horincar, Georgiana, Ghinea, Ioana Otilia, Furdui, Bianca, Bahrim, Gabriela-Elena, Barbu, Vasilica, Balanescu, Fanica, Favier, Lidia, Dinica, Rodica-Mihaela
• Format: Article
• Language: English
• Subjects: Activated carbon; Alkynes; Biocatalysts; Bioconversion; Biomass; Biosynthesis; Buffer solutions; Carbonyls; Cascade chemical reactions; Catalysis; Catalysts; Chemical reactions; Chemical Sciences; Chemicals; Cultivation; Cycloaddition; Enzymes; Fermentation; Fluorescence; Germination; indolizine; Metabolites; Organic chemistry; Parameter sensitivity; Pharmaceutical industry; Physiological effects; Physiology; Reagents; Room temperature; Scanning microscopy; Seeds; Toxicity testing; whole–cell biocatalysis; Yarrowia lipolytica; Yeast
• ISSN: 2073-4344; 2073-4344
• DOI: 10.3390/catal10060629

A series of yeast strains was tested in order to evaluate their catalytic potential in biocatalysis of one-pot indolizine’s synthesis. Yeast cultivation was performed in a submerged system at 28 °C for 72 h at 180 rpm. An assessment of the reagents’ toxicity on yeast viability and metabolic functionality concluded that the growth potential of three Yarrowia lipolytica strains were least affected by the reactants compared to the other yeast strains. Further, crude fermentation products (biomass and cell-free supernatant)—obtained by submerged cultivation of these yeasts—were used in multistep cascade reactions for the production of fluorescent indolizine compounds with important biologic activities. A whole–cell catalyzed multicomponent reaction of activated alkynes, α-bromo-carbonyl reagents and 4,4′-bipyridine, at room temperature in buffer solution led to the efficient synthesis of bis-indolizines 4a, 4b and 4c, in good-to-excellent yields (47%–77%). The metabolites of the selected Y. lipolytica strains can be considered effective biocatalysts in cycloaddition reactions and the high purity and bioconversion yields of the synthesized indolizines indicates a great potential of this type of “green” catalysts. Seeds of Triticum estivum L. were used to investigate the impact of the final products on the germination and seedling growth. The most sensitive physiological parameters suggest that indolizines, at the concentrations tested, have non-toxic effect on germination and seedling growth of wheat, fact also confirmed by confocal laser scanning microscopy images.