Metabolic Engineering of Saccharomyces cerevisiae for Enhanced Carotenoid Production From Xylose-Glucose Mixtures

Abstract

Co-utilization of xylose and glucose from lignocellulosic biomass is an economically feasible bioprocess for chemical production. Many strategies have been implemented for efficiently assimilating xylose which is one of the predominant sugars of lignocellulosic biomass. However, there were few reports about engineering Saccharomyces cerevisiae for carotenoid production from xylose-glucose mixtures. Herein, we developed a platform for facilitating carotenoid production in S. cerevisiae by fermentation of xyloseglucose mixtures. Firstly, a xylose assimilation pathway with mutant xylose reductase (XYL1m), xylitol dehydrogenase (XYL2), and xylulokinase (XK) was constructed for utilizing xylose. Then, introduction of phosphoketolase (PK) pathway, deletion of Pho13 and engineering yeast hexose transporter Gal2 were conducted to improve carotenoid yields. The final strain SC105 produced a 1.6-fold higher production from mixed sugars than that from glucose in flask culture. In fed-batch fermentation with continuous feeding of mixed sugars, carotenoid production represented a 2.6-fold higher. To the best of our knowledge, this is the first report that S. cerevisiae was engineered to utilize xyloseglucose mixtures for carotenoid production with a considerable high yield. The present study exhibits a promising advantage of xylose-glucose mixtures assimilating strain as an industrial carotenoid producer from lignocellulosic biomass.

Yeast-Based Biosynthesis of Natural Products From Xylose

“…Currently, production of vitamin A, protopanaxadiol, p -coumaric acid, carotenoid, and other natural products has been achieved in Sa. cerevisiae by fermentation on xylose ( Table 1 ; Kwak et al, 2017 ; Borja et al, 2019 ; Su et al, 2020 ). For instance, a lycopene biosynthetic pathway consisting of CrtE , CrtB , and CrtI was introduced into xylose-fermenting Sa.…”

“…The PK pathway consisting of xylulose-5-phosphate phosphoketolase (xPK) and phosphotransacetylase (PTA) was further introduced to directly convert xylulose-5-phosphate into acetyl-CoA. The resultant strain produced 1.6-fold more lycopene using the mixture of glucose and xylose than using glucose alone ( Su et al, 2020 ). In another case, squalene-producing recombinant Sa.…”

Sustainable Production of Microbial Isoprenoid Derived Advanced Biojet Fuels Using Different Generation Feedstocks: A Review

“…A number of recombinant S. cerevisiae strains with the ability to metabolize xylose have been successfully constructed. S. cerevisiae was recently engineered for the production of a carotenoid, lycopene, from a mixed glucose-xylose substrate (Su et al, 2020). Through engineering heterologous pathways for xylose consumption and lycopene synthesis a maximum titer of 903 mg/L was achieved in fed-batch culture on the mixed substrate (Su et al, 2020).…”

“…S. cerevisiae was recently engineered for the production of a carotenoid, lycopene, from a mixed glucose-xylose substrate (Su et al, 2020). Through engineering heterologous pathways for xylose consumption and lycopene synthesis a maximum titer of 903 mg/L was achieved in fed-batch culture on the mixed substrate (Su et al, 2020). However, preference for glucose and slow and repressive consumption of xylose during coconsumption of the two sugars remain major bottlenecks (Chen et al, 2015).…”

Transcriptome Analysis Reveals a Promotion of Carotenoid Production by Copper Ions in Recombinant Saccharomyces cerevisiae

“…Previously, we engineered a synthetic pathway for carotenoid biosynthesis (using lycopene as the model carotenoid) in S. cerevisiae and gained a higher production using the YPM media [ 11 , 12 ]. In this study, we aim to determine the impacts of nutritional components on the carotenoid yield of BL03-D-4 generated from our prior work, and then attempt to uncover the potential mechanisms of the promoted carotenoid production associated with supplementation of nutritional components by transcriptome analysis.…”