Τίτλος:
Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Terpenes are a large class of natural products, many of which are used in cosmetics, pharmaceuticals, or biofuels. However, terpene[U+05F3]s industrial application is frequently hindered by limited availability of natural sources or low yields of chemical synthesis. In this report, we developed a modular platform based on standardized and exchangeable parts to reproduce and potentially expand the diversity of terpene structures in Saccharomyces cerevisiae. By combining different module-specific parts, we exploited the substrate promiscuity of class I diterpene synthases to produce an array of labdane-type scaffolds. These were subsequently modified by a scaffold decoration module consisting of a mutant library of a promiscuous cytochrome P450 to afford a range of hydroxylated diterpenes. Further P450 protein engineering yielded dedicated and efficient catalysts for specific products. Terpenes produced include precursors of pharmacologically important compounds, molecules that are difficult to obtain from natural sources, or new natural products. The approach described here provides a platform on which additional gene mining, combinatorial biosynthesis, and protein engineering efforts can be integrated to sustainably explore the terpene chemical space. © 2014 International Metabolic Engineering Society.
Συγγραφείς:
Ignea, C.
Ioannou, E.
Georgantea, P.
Loupassaki, S.
Trikka, F.A.
Kanellis, A.K.
Makris, A.M.
Roussis, V.
Kampranis, S.C.
Περιοδικό:
Metabolic Engineering
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
Biochemical engineering; Biochemistry; Biosynthesis; Genetic engineering; Olefins; Proteins; Terpenes; Uranium; Yeast, Chemical diversity; Combinatorial biosynthesis; Cytochrome p450; Diterpene synthases; Efficient catalysts; Isoprenoids; Mutant libraries; Protein engineering, Metabolic engineering, cytochrome P450; diterpene; synthetase; terpene; diterpene; Saccharomyces cerevisiae protein, Article; biosynthesis; catalyst; gene; hydroxylation; mutant; nonhuman; priority journal; protein engineering; Saccharomyces cerevisiae; yeast; genetics; metabolism, Saccharomyces cerevisiae, Cytochrome P-450 Enzyme System; Diterpenes; Hydroxylation; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
DOI:
10.1016/j.ymben.2014.12.001
