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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Food Microbiology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1636554

A transcriptome-based and genetically modified strategy for balancing cell growth and astaxanthin synthesis in Phaffia rhodozyma

Provisionally accepted
Jianping  JiaJianping JiaChenxi  YeChenxi YeSainan  JinSainan JinQingqing  LiQingqing LiZhengyi  PanZhengyi PanWen  WenWen WenGuoliang  BaoGuoliang Bao*
  • Hangzhou Medical College, Hangzhou, China

The final, formatted version of the article will be published soon.

Astaxanthin is a strong antioxidant and is widely applied in food industry. The yeast Phaffia rhodozyma is an ideal microbial for astaxanthin production. However, the nitrogen-deficiency stress, which is beneficial for astaxanthin synthesis, often impairs cell growth, leading to low productivity. In this study, an imbalance between cellular growth and astaxanthin synthesis in P. rhodozyma under nitrogen-deficiency (H) and nitrogen-sufficiency (L) conditions was identified. A comparative RNA-seq transcriptome analysis between the H and L groups revealed well-discriminated patterns. The differentially expressed genes (DEGs) indicated that the regulation of nitrogen-deficiency dose not directly occur in the astaxanthin biosynthesis pathway, but rather at the global cellular level, involving processes such as central and energy metabolism, antioxidative stress responses, signal transduction, competitive metabolic pathways, and material transportation. Based on these findings, a regulatory mechanism is proposed, which involves cellular sensing of nitrogen sources in the medium, alterations in signaling pathways that direct effectors, and the regulation of multiple downstream target genes through post-translational modifications, protein interactions, gene transcription, as well as protein and metabolite levels. Six DEGs were overexpressed in the wild strain (WT) of P. rhodozyma, and the mutants M2 and M6, expressing the NHEJ gene for DNA repair and the ferric reductase gene, showed higher biomass and astaxanthin content compared to the WT strain under nitrogen-deficient conditions. However, the remaining mutants exhibited unchanged or even reduced biomass and astaxanthin productivity. Subsequently, a co-expression mutant (M7) carrying the two DEGs was constructed. This mutant exhibited further increases in both biomass and astaxanthin content, with 61.5% and 133.3% higher yields than the WT strain, and a 265.8% increase in final astaxanthin production.

Keywords: Phaffia rhodozyma, astaxanthin, Nitrogen-deficiency, Oxidative Stress, non-homologous end-joining, ferric reductase

Received: 28 May 2025; Accepted: 22 Aug 2025.

Copyright: © 2025 Jia, Ye, Jin, Li, Pan, Wen and Bao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Guoliang Bao, Hangzhou Medical College, Hangzhou, China

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