A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of beta-carotene

作者：Larroude, Macarena; Celinska, Ewelina; Back, Alexandre; Thomas, Stephan; Nicaud, Jean-Marc; Ledesma-Amaro, Rodrigo^*

来源：Biotechnology and Bioengineering, 2018, 115(2): 464-472.

DOI：10.1002/bit.26473

• beta-carotene
• golden gate
• metabolic engineering
• promoter shuffling
• synthetic biology
• Yarrowia lipolytica

The increasing market demands of -carotene as colorant, antioxidant and vitamin precursor, requires novel biotechnological production platforms. Yarrowia lipolytica, is an industrial organism unable to naturally synthesize carotenoids but with the ability to produce high amounts of the precursor Acetyl-CoA. We first found that a lipid overproducer strain was capable of producing more beta-carotene than a wild type after expressing the heterologous pathway. Thereafter, we developed a combinatorial synthetic biology approach base on Golden Gate DNA assembly to screen the optimum promoter-gene pairs for each transcriptional unit expressed. The best strain reached a production titer of 1.5g/L and a maximum yield of 0.048g/g of glucose in flask. beta-carotene production was further increased in controlled conditions using a fed-batch fermentation. A total production of beta-carotene of 6.5g/L and 90mg/g DCW with a concomitant production of 42.6g/L of lipids was achieved. Such high titers suggest that engineered Y. lipolytica is a competitive producer organism of beta-carotene.

• 出版日期2018-2