Abstract
Genome-scale metabolic models embody a significant advantage of systems biology since their applications as metabolic flux simulation models enable predictions for the production of industrially-interesting metabolites. The biotechnological production of lycopene from Yarrowia lipolytica is an emerging scope that has not been fully scrutinized, especially for what concerns cultivation conditions of newly generated engineered strains. In this study, by combining flux balance analysis (FBA) and Plackett-Burman design, we screened chemicals for lycopene production from a metabolically engineered strain of Y. lipolytica. Lycopene concentrations of 126 and 242 mg/L were achieved correspondingly from the FBA-independent and the FBA-assisted designed media in fed-batch cultivation mode. Transcriptional studies revealed upregulations of heterologous genes in media designed according to FBA, thus implying the efficiency of model predictions. Our study will potentially support upgraded lycopene and other terpenoids production from existing or prospect bioengineered strains of Y. lipolytica and/or closely related yeast species.
Highlights
Carotenoids represent a subcategory of tetraterpenoid pigmented lipid compounds made by plants and various fungi and bacteria [1]
We screened a set of chemicals without considering the flux balance analysis (FBA)
The results showed that FBA-predicted and Plackett-Burman design (PBD) screened factors differentially affected genes of the terpenoids backbone, zwf and crt genes
Summary
Carotenoids represent a subcategory of tetraterpenoid pigmented lipid compounds made by plants and various fungi and bacteria [1]. Exemplified by ß-carotene, lycopene, astaxanthin, zeaxanthin, fucoxanthin, ß-cryptoxanthin, canthaxanthin, lutein, and crocetin, compounds of the carotenoids family handle a diversity of bright colors such as yellow, red, purple, and orange [2,3]. Lycopene is a bioactive phytochemical of this vast family of carotenoids that has gained much concerns these recent years because of its commercial attributes and due to its biofunctionality [4]. Synthesized on one hand, by plants like tomato, watermelon, guava, papaya, apricots, pink grapefruits, and red oranges and on the other hand by carotenogenic microorganisms, lycopene is essential for the human body given that it can only be provided through its ingestion under multiple forms such as food or drugs. Lycopene is recognized as a strong cancer chemo-preventive agent [9,10] and has been found to have cardio-protective, antioxidant, and anti-inflammatory effects [11]
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