Astaxanthin is widely used in food, feed and nutraceutical industries. Xanthophyllomyces dendrorhous is one of the most promising natural sources of astaxanthin. However, the astaxanthin yield in the wild-type X. dendrorhous is considered low for industrial application. In the present study, X. dendrorhous ATCC 66272 was subjected to two-staged mutagenesis: (i) UV light and (ii) N-methyl-N 0 -nitro-N-nitroso-guanidine (NTG) toward attaining higher astaxanthin yield. The UV-irradiation mutant, X. dendrorhous SK974 showed 1.7-fold (1.07 mg/g) higher astaxanthin production as compared with the wild-type strain (0.65 mg/g). The UV mutant strain was then treated with NTG, designated as X. dendrorhous SK984, displayed further 1.4-fold (1.45 mg/g) higher astaxanthin production. Furthermore, the oak leaf extract (5%, v/v) and inorganic phosphate (KH 2 PO 4 , 3 mM) supplementation resulted about 1.4-fold (1.98 mg/g) higher astaxanthin production as compared with control (1.45 mg/g) in X. dendrorhous SK984. These findings serve as a platform suggesting that intersecting approaches might be aimed toward systematically enhanced astaxanthin production.

Background: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to efficiently treat desmoid tumor. However, molecular mechanism of why imatinib works remains poorly understood. Here, we describe the potential roles of NOTCH2 and HES1 in association with clinical response to imatinib as in genome and transcriptome levels. Methods: We identified all somatic mutations in coding and non-coding regions via whole genome sequencing using desmoid tumor samples. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale Whole-genome sequencing (WGS) and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, 4 (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥1 year. With gene-wise functional analyses, we detected significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on PCAWG data analyses, NOTCH2 mutations affect its expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders Conclusions: Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, which provides an important therapeutic consideration for desmoid tumor. Trial Registration: ClinicalTrials.gov, NCT02495519, Registered July 13, 2015- Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02495519