Improvements in Taxol Biosynthesis by Metabolic Engineering: Recent Trends

Abstract

AbstractTaxol is one of the major anti-cancer drugs that is derived from plant sources. It was first isolated from Taxus sp. However, due to the limited accessibility of taxol, it has been a major challenge to use it in the field of clinical medicine. Researchers have continuously tried to improve the yield of taxol from alternative sources. Many metabolically engineered approaches have been utilized for the isolation of taxol in a good amount of concentration. In this article, we explore the biosynthetic pathways of taxol along with its production within the endophytic fungi. The CRISPR/Cas have been used to develop a better synthesis of taxol within endophytic fungi. Sterol inhibitors have been also used for directing the GGPP pool for the synthesis of paclitaxel or taxol. In E. coli, taxadiene-5α-hydroxylase-based improvement process was carried out and this engineered mechanism allowed specificity towards the selection of taxa-4(20)-11(12)-diene, which is an alternative cyclization product that helps in the formation of taxol. In Aspergillus flavipes, conjugation of taxol with porphyrin enhanced taxol activity towards liver carcinoma (HepG2) 1.5-fold. In Bacillus subtilis, a strain was engineered with txs + crtE + SDFHCEGA that showed 83 times higher levels of taxadiene within its cells. Furthermore, yeast cells were modified in such a way that taxadiene synthase from Sulfolobus acidocaldarius showed a 40-fold increase in the expression level of taxadiene as compared to the CEN9 strain. Therefore, this chapter briefly explores several alternative engineered sources for taxol biosynthesis.KeywordsTaxolTaxadieneMetabolic engineeredGeranylgeranyl pyrophosphateFarnesyl pyrophosphateCancer