Metabolic flux analysis of Xanthophyllomyces dendrorhous metabolism to understand the production of astaxanthin
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Abstract
Carotenoid production by microorganisms, contrary to chemical synthesis, could fulfill the in-creasing demand for human consumption. The yeastX. drendrorhousis one of the most promis-ing and economically attractive microorganisms for industrial production of astaxanthin. Themetabolic pathway through which this yeast synthesize this valuable carotenoid is known. How-ever, the complex mechanisms that are involved in the process, the distribution of the metabolicfluxes and the rates at which the pathways work, remain unknown. Several studies have provideddifferent approaches to manipulate and improve carotenoid production inX. dendrorhousfromclassical mutagenesis to genetic engineering of the complete pathway covering improved precur-sor supply for carotenogenesis, enhanced metabolite flow into the pathway, and manipulating therelation C/N in the culture medium. However, it has not been reported quantitatively how nutri-ents, from the central metabolism and other pathways, converge in the carotenoids biosynthesis.In this study, the metabolism ofX. dendrorhousgrowing in a continuous culture, under two am-monia conditions, Limited (L) and Non-limited (NL). The metabolic flux analysis (MFA) allowedto understand the distribution the intracellular fluxes along the different metabolic pathways eval-uated, but most important, it elucidated that by limiting the ammonia assimilation flux(L= 0.002±1.1 E-05; NL= 0.004±4.3 E-05; g/gcellh), a promotion of the astaxanthin formation flux wasobtained (L= 86.4±0.6; NL= 0; ug/gcellh). This first approach will help to set a deeper studyin order to understand the metabolic pathways that regulate the flux towards the astanxanthinbiosynthesis