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Lycopene over-accumulation by disruption of the negative regulator gene crgA in Mucor circinelloides

  • Applied Genetics and Molecular Biotechnology
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Abstract

Lycopene has become one of the most interesting antioxidant compounds, especially in relation to human health. This work describes a genetic strategy to modify the carotenoid biosynthesis pathway to develop a lycopene-overproducing strain. The crgA gene, a negative regulator of carotenogenesis, was disrupted in the Mucor circinelloides strain MU202, which lacks the lycopene cyclase activity and accumulates lycopene instead of β-carotene. The resultant strain, MU224, demonstrated increased transcriptional levels of the carotenogenesis structural genes carRP and carB compared to the parental strain MU202. As a consequence, strain MU224 accumulated 5 mg/g of dry weight of cells in liquid cultures, a sevenfold increase with respect to the parental strain. Moreover, when lycopene production was examined in a complex enriched medium, biomass increased tenfold compared to that obtained in synthetic minimal medium. In this complex medium, the production rate of lycopene by strain MU224 reached 54 g/l. These results illustrate how a combination of genetic manipulation and optimized culture conditions can be utilized to enhance the production of commercially desirable compounds such as lycopene.

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Acknowledgments

We thank J. A. Madrid for technical assistance. This work was funded by the Spanish Ministerio de Ciencia y Tecnología (BMC2003-01017) and the Fundación Séneca PB/73/FS/02 (Murcia, Spain). F. E. Nicolas-Molina was supported by a graduate fellowship from the Spanish Ministerio de Educación y Cultura.

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Correspondence to Francisco E. Nicolás-Molina.

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Nicolás-Molina, F.E., Navarro, E. & Ruiz-Vázquez, R.M. Lycopene over-accumulation by disruption of the negative regulator gene crgA in Mucor circinelloides . Appl Microbiol Biotechnol 78, 131–137 (2008). https://doi.org/10.1007/s00253-007-1281-5

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