期刊
MICROORGANISMS
卷 9, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/microorganisms9040838
关键词
Yarrowia lipolytica; pyomelanin; chassis strain; aromatic amino acids
类别
资金
- European Union [720824]
In this study, the yeast Yarrowia lipolytica was engineered to overproduce pyomelanin by optimizing a chassis strain to increase homogentisic acid synthesis. The overexpression of the 4HPPD gene led to significantly higher pyomelanin yields, with the pathway being strongly induced by phenylalanine supplementation.
The yeast Yarrowia lipolytica naturally produces pyomelanin. This pigment accumulates in the extracellular environment following the autoxidation and polymerization of homogentisic acid, a metabolite derived from aromatic amino acids. In this study, we used a chassis strain optimized to produce aromatic amino acids for the de novo overproduction of pyomelanin. The gene 4HPPD, which encodes an enzyme involved in homogentisic acid synthesis (4-hydroxyphenylpyruvic acid dioxygenase), was characterized and overexpressed in the chassis strain with up to three copies, leading to pyomelanin yields of 4.5 g/L. Homogentisic acid is derived from tyrosine. When engineered strains were grown in a phenylalanine-supplemented medium, pyomelanin production increased, revealing that the yeast could convert phenylalanine to tyrosine, or that the homogentisic acid pathway is strongly induced by phenylalanine.
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