Metabolic Engineering of Saccharomyces cerevisiae for Production of Shinorine, a Sunscreen Material, from Xylose

Abstract

Shinorine, a mycosporine-like amino acid (MAA), is a small molecule sunscreen produced in some bacteria. In this study, by introducing shinorine biosynthetic genes from cyanobacteria Nostoc punctiform into Saccharomyces cerevisiae, we successfully constructed yeast strains capable of producing shinorine. Sedoheptulose 7-phosphate (S7P), an intermediate of the pentose phosphate pathway, is a key substrate for shinorine biosynthesis. To increase the S7P pool, xylose, which is assimilated via the pentose phosphate pathway, was used as a carbon source after introducing xylose assimilation genes from Schef fersomyces stipitis into the shinorine-producing strain. The resulting xylose-fermenting strain produced a trace amount of shinorine when cells were grown in glucose, but shinorine production was dramatically increased by adding xylose in the medium. Shinorine production was further improved by modulating the pentose phosphate pathway through deleting TAL1 and overexpressing STB5 and TKL1. The final engineered strain JHYS17−4 produced 31.0 mg/L (9.62 mg/g DCW) of shinorine in the optimized medium containing 8 g/L of xylose and 12 g/L of glucose, demonstrating that S. cerevisiae is a promising host to produce this natural sunscreen material.

Effects of overexpression of STB5 in Saccharomyces cerevisiae on fatty acid biosynthesis, physiology and transcriptome

“…overexpressed STB5 as a means to enhance the flux through the PPP, and found the strategy positively stimulated shinorine production (Park et al . 2018). However, even while Kim et al .…”

Yeast-Based Biosynthesis of Natural Products From Xylose

“…This strain produced 242 mg/L of p-coumaric acid from xylose while the titer was only 5.35 mg/L on glucose. Moreover, a xylose-fermenting strain expressing the biosynthetic pathway of shinorine, a natural sunscreen material, produced a trace amount of shinorine in glucose, whereas the titer was dramatically increased by adding xylose in the medium (Park et al, 2019). This interesting result was related to enhanced PPP flux triggered by xylose and abundant supply of sedoheptulose-7-phosphate, which is the preliminary precursor for the synthesis of shinorine.…”

Xylose Assimilation for the Efficient Production of Biofuels and Chemicals by Engineered Saccharomyces cerevisiae

“…[21] Interestingly, a recent study took advantage of the S7P accumulation and produced 31.0 mg L −1 of shinorine, a sunscreen material that requires S7P as a precursor in its biosynthesis, from xylose and glucose mixtures ( Figure 2). [63] To improve the availability of S7P, Park et al deleted TAL1 alongside overexpressing STB5 and TKL1 in the xylose utilization strain that expressed the shinorine biosynthetic pathway. [63] Besides shinorine, S7P can serve as a promising gateway to a diverse set of bioactive metabolites including sedoheptulose, gadusol, validamycin, and cetoniacytone A.…”

“…[63] To improve the availability of S7P, Park et al deleted TAL1 alongside overexpressing STB5 and TKL1 in the xylose utilization strain that expressed the shinorine biosynthetic pathway. [63] Besides shinorine, S7P can serve as a promising gateway to a diverse set of bioactive metabolites including sedoheptulose, gadusol, validamycin, and cetoniacytone A. These metabolites are valuable as nutritional supplements, organic sunscreens, fungicides, and antibiotics.…”

“…The above‐mentioned traits of xylose metabolism combined with recent advancements in simultaneous co‐utilization would facilitate efficient and economic bioconversion of cellulosic substrates. In particular, the production of certain chemicals, such as xylitol [ 59 ] and shinorine, [ 63 ] benefits from dual‐substrate usage wherein one substrate sustains cell growth and the other is devoting to biosynthesis. [ 97 ] Collectively, to boost the lignocellulosic biomass‐based bioeconomy, much attention is required to enhance xylose‐utilizing efficiency via reprogramming cellular regulatory networks, to attain robust co‐consumption of xylose and other cellulosic carbon sources under industrial conditions, and to exploit xylose‐induced metabolic rerouting and respiratory response for producing diverse chemicals.…”