Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

Abstract

MDPI Open Access Journals zoom_out_map search menu Journals Molecules Volume 25 Issue 13 10.3390/molecules25133000 molecules-logo Submit to this Journal Review for this Journal Edit a Special Issue ► Article Menu Open AccessReview Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation by Ashraf S.A. El-Sayed 1,*,Manal T. El-Sayed 1,Amgad M. Rady 2,Nabila Zein 3,Gamal Enan 1,Ahmed Shindia 1,Sara El-Hefnawy 1,Mahmoud Sitohy 4OrcID andBasel Sitohy 5,6,*OrcID 1 Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt 2 Faculty of Biotechnology, October University for Modern Sciences and Arts, Cairo 12566, Egypt 3 Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt 4 Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt 5 Department of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, Sweden 6 Department of Radiation Sciences, Oncology, Umeå University, SE-90185 Umeå, Sweden * Authors to whom correspondence should be addressed. Molecules 2020, 25(13), 3000; https://doi.org/10.3390/molecules25133000 Received: 24 May 2020 / Revised: 17 June 2020 / Accepted: 23 June 2020 / Published: 30 June 2020 (This article belongs to the Special Issue Drug Discovery and Development Based on Native/Engineered Microorganisms) View Full-Text Download PDF Browse Figures Cite This Paper Abstract Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids “Taxol” is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.