Natural and engineered production of taxadiene with taxadiene synthase

• Published in: Biotechnology and bioengineering Vol. 112; no. 2; pp. 229 - 235
• Main Authors: Soliman, Sameh, Tang, Yi
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2015; Wiley Subscription Services, Inc
• Subjects: Alkenes - chemistry; Alkenes - metabolism; Bioengineering; Biosynthesis; Biotechnology; Catalytic Domain; Control; Crystal structure; Diterpenes - chemistry; Diterpenes - metabolism; E coli; Enzymes; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; fungus; Isomerases - chemistry; Isomerases - genetics; Isomerases - metabolism; metabolic engineering; Metabolic Engineering - methods; metabolic regulation; Microorganisms; Pathways; Plants (organisms); protein engineering; taxadiene synthase; Taxus; Taxus - chemistry; Taxus - genetics; Taxus - metabolism; taxadiene synthase; protein engineering; metabolic engineering; Taxus; fungus; metabolic regulation
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.25468

ABSTRACT Taxadiene synthase (TXS) is the rate‐limiting enzyme in the biosynthesis of paclitaxel, an important anticancer compound. TXS catalyzes the conversion of the diterpene precursor geranylgeranyl pyrophosphate (GGPP) into the diterpene taxadiene. Due to the importance of taxadiene in the overall biosynthetic pathway of paclitaxel biosynthesis, the enzyme TXS has been the subject of intense scientific and engineering investigations. The crystal structure of TXS was recently elucidated, thereby providing an atomic blueprint for future protein engineering efforts. Metabolic engineering of TXS for taxadiene product in different microbial and plant organisms have also been extensively performed, culminating in the high‐titer production in Escherichia coli. Additional aspects of taxadiene production by TXS will be discussed in the review, including metabolic regulation in native host and possible production by endophytic fungal hosts. Biotechnol. Bioeng. 2015;112: 229–235. © 2014 Wiley Periodicals, Inc. Taxadiene synthase (TXS) catalyzes the first‐committed step in paclitaxel biosynthetic pathway by cyclizing GGPP to taxadiene. Metabolic engineering of TXS has been successfully demonstrated in microbes and higher plants.