Browsing by Author "Mehrabi, Ali Ashraf"
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Item Biotechnological production of flavonoids: an update on plant metabolic engineering, microbial host selection and genetically encoded biosensorsMarsafari, Monireh; Samizadeh, Habibollah; Rabiei, Babak; Mehrabi, Ali Ashraf; Koffas, Mattheos; Xu, PengFlavonoids represent a diversified family of phenylpropanoid-derived plant secondary metabolites. They are widely found in fruits, vegetables and medicinal herbs and plants. There has been increasing interest on flavonoids because of their proven bioactivity associated with anti-obesity, anti-cancer, anti-inflammatory, anti-diabetic activity and the prevention of aging-related chronic conditions, such as nervous and cardiovascular disease. Low bioavailability of flavonoids is a major challenge restricting their wide applications. Due to safety and economic issues, traditional plant extraction or chemical synthesis could not provide a scalable route for large-scale production of flavonoids. Alternatively, reconstruction of biosynthetic gene clusters in plants and industrially relevant microbes offer significant promise for discovery and scalable synthesis of flavonoids. This review provides an update on biotechnological production of flavonoids. We summarized the recent advances on plant metabolic engineering, microbial host and genetically encoded biosensors. Plant metabolic engineering holds the promise to improve the yield of specific flavonoids and expand the chemical space of novel flavonoids. The choice of microbial host provides the cellular chassis that could be tailored for various stereo- or regio-selective chemistries that are crucial for their bioactivities. When coupled with transcriptional biosensing, genetically encoded biosensors could be welded into cellular metabolism to achieve high throughput screening or dynamic carbon flux re-allocation to deliver efficient and robust microbial workhorse. The convergence of these technologies will translate the vast majority of plant genetic resources into valuable flavonoids with pharmaceutical/nutraceutical values in the foreseeable future.Item The optimization of Naringenin biosynthesis pathway using Yarrowia lipolitica cell culture(Kharazmi University, 2020-06-30) Marsafari, Monireh; Lahiji, Habibollah Samizadeh; Rabiei, Babak; Mehrabi, Ali Ashraf; Lv, Yongkun; Xu, PengYarrowia lipolytica, as a good cell factory to speed up the production of plant pharmaceutical components, has been considered to be one of the most important and attractive micro-organisms in recent years, due to its high secretion capacity, limited glycosylation, large range of genetic markers and molecular tools. Naringenin, as a central core of flavonoids production, plays important roles both in plants and in the treatment of different types of human diseases. For this purpose, specific naringenin biosynthesis genes from different origins were selected and introduced after comparative expression profiling in Y. lipolytica. This research indicated that chs plays the main role in the production of naringenin, so the increase copy number of this gene in each construct was investigated. The HPLC results confirmed that the construct with 5 copy numbers of chs resulted in 7.14 fold increase of naringenin extracellular titer to 90.16 mg/L in shake flask cultures. The results reported in this study demonstrated that sufficient knowledge of genes involved in the specific biosynthesis pathway, synthetic gene pathway and using Y. lipolytica as a capable and cheap host could help bioengineers to produce significant amounts of pharmaceutical components.