Delta-tocotrienol
as a vitamin E isomer has received much attention
because of its diverse biomedical applications. Microbial biosynthesis
of delta-tocotrienol is a promising strategy for its economic and
environmental advantages. Here, we accomplished complete biosynthesis
of delta-tocotrienol in Saccharomyces cerevisiae from glucose. We first constructed and incorporated a heterologous
pathway into the genome of S. cerevisiae by incorporating the genes hpd (from Pseudomonas putida KT2440), hpt (from Synechocystis sp. PCC 6803), and vte1 (from Arabidopsis thaliana) for the
biosynthesis of delta-tocotrienol. We further enhanced the biosynthesis
of the precursor geranylgeranyl diphosphate by overexpressing the thmg1 and ggppssa (from Sulfolobus acidocaldarius) genes, leading to a production
titer of delta-tocotrienol of 1.39 ± 0.01 mg/L. Finally, we optimized
the fermentation medium using the response surface methodology, enabling
a high-titer production of delta-tocotrienol (3.56 ± 0.25 mg/L),
∼2.6-fold of that of the initial culture medium. Fed-batch
fermentation in a 2 L fermenter was further used to enhance the production
titer of delta-tocotrienol (4.10 ± 0.10 mg/L). To the best of
our knowledge, this is the first report on the de novo biosynthesis
of delta-tocotrienol in S. cerevisiae, and the highest titer obtained for microbial production of delta-tocotrienol.
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