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.

Compared to the existing noninvasive methods, temporal interference (TI) current stimulation is an emerging noninvasive neuromodulation technique that can improve the ability to focus an electrical field on a target nerve. Induced TI field distribution depends on the anatomical structure of individual neurons, and thus the electrode and current optimization to enhance the field focus must reflect these factors. The current study presents a TI field optimization framework for focusing the stimulation energy on the target tibial nerve through extensive electrical simulations, factoring in individual anatomical differences. We conducted large-scale in-silico experiments using realistic models based on magnetic resonance images of human subjects to evaluate the effectiveness of the proposed methods for tibial nerve stimulation considering overactive bladder (OAB) treatment. The electrode position and current intensity were optimized for each subject using an automated algorithm, and the field-focusing performance was evaluated based on the maximum intensity of the electric fields induced at the target nerve compared with the electric fields in the neighboring tissues. Using the proposed optimization framework, the focusing ability increased by 12% when optimizing the electrode position. When optimizing both the electrode position and current, this capability increased by 11% relative to electrode position optimization alone. These results suggest the significance of optimizing the electrode position and current intensity for focusing TI fields at the target nerve. Our electrical simulation-based TI optimization framework can be extended to enable personalized peripheral nerve stimulation therapy to modulate peripheral nerves.