Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast

Abstract Plants synthesize numerous specialized metabolites (also termed natural products) to mediate dynamic interactions with their surroundings. The complexity of plant specialized metabolism is the result of an inherent biosynthetic plasticity rooted in the substrate and product promiscuity of t...

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Autores principales:	Codruta Ignea, Anastasia Athanasakoglou, Aggeliki Andreadelli, Maria Apostolaki, Minas Iakovides, Euripides G. Stephanou, Antonios M. Makris, Sotirios C. Kampranis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b63b2a195d8b415fa01df1947fdecad9
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spelling	oai:doaj.org-article:b63b2a195d8b415fa01df1947fdecad92021-12-02T12:32:56ZOvercoming the plasticity of plant specialized metabolism for selective diterpene production in yeast10.1038/s41598-017-09592-52045-2322https://doaj.org/article/b63b2a195d8b415fa01df1947fdecad92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09592-5https://doaj.org/toc/2045-2322Abstract Plants synthesize numerous specialized metabolites (also termed natural products) to mediate dynamic interactions with their surroundings. The complexity of plant specialized metabolism is the result of an inherent biosynthetic plasticity rooted in the substrate and product promiscuity of the enzymes involved. The pathway of carnosic acid-related diterpenes in rosemary and sage involves promiscuous cytochrome P450s whose combined activity results in a multitude of structurally related compounds. Some of these minor products, such as pisiferic acid and salviol, have established bioactivity, but their limited availability prevents further evaluation. Reconstructing carnosic acid biosynthesis in yeast achieved significant titers of the main compound but could not specifically yield the minor products. Specific production of pisiferic acid and salviol was achieved by restricting the promiscuity of a key enzyme, CYP76AH24, through a single-residue substitution (F112L). Coupled with additional metabolic engineering interventions, overall improvements of 24 and 14-fold for pisiferic acid and salviol, respectively, were obtained. These results provide an example of how synthetic biology can help navigating the complex landscape of plant natural product biosynthesis to achieve heterologous production of useful minor metabolites. In the context of plant adaptation, these findings also suggest a molecular basis for the rapid evolution of terpene biosynthetic pathways.Codruta IgneaAnastasia AthanasakoglouAggeliki AndreadelliMaria ApostolakiMinas IakovidesEuripides G. StephanouAntonios M. MakrisSotirios C. KampranisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Codruta Ignea Anastasia Athanasakoglou Aggeliki Andreadelli Maria Apostolaki Minas Iakovides Euripides G. Stephanou Antonios M. Makris Sotirios C. Kampranis Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
description	Abstract Plants synthesize numerous specialized metabolites (also termed natural products) to mediate dynamic interactions with their surroundings. The complexity of plant specialized metabolism is the result of an inherent biosynthetic plasticity rooted in the substrate and product promiscuity of the enzymes involved. The pathway of carnosic acid-related diterpenes in rosemary and sage involves promiscuous cytochrome P450s whose combined activity results in a multitude of structurally related compounds. Some of these minor products, such as pisiferic acid and salviol, have established bioactivity, but their limited availability prevents further evaluation. Reconstructing carnosic acid biosynthesis in yeast achieved significant titers of the main compound but could not specifically yield the minor products. Specific production of pisiferic acid and salviol was achieved by restricting the promiscuity of a key enzyme, CYP76AH24, through a single-residue substitution (F112L). Coupled with additional metabolic engineering interventions, overall improvements of 24 and 14-fold for pisiferic acid and salviol, respectively, were obtained. These results provide an example of how synthetic biology can help navigating the complex landscape of plant natural product biosynthesis to achieve heterologous production of useful minor metabolites. In the context of plant adaptation, these findings also suggest a molecular basis for the rapid evolution of terpene biosynthetic pathways.
format	article
author	Codruta Ignea Anastasia Athanasakoglou Aggeliki Andreadelli Maria Apostolaki Minas Iakovides Euripides G. Stephanou Antonios M. Makris Sotirios C. Kampranis
author_facet	Codruta Ignea Anastasia Athanasakoglou Aggeliki Andreadelli Maria Apostolaki Minas Iakovides Euripides G. Stephanou Antonios M. Makris Sotirios C. Kampranis
author_sort	Codruta Ignea
title	Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
title_short	Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
title_full	Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
title_fullStr	Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
title_full_unstemmed	Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
title_sort	overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b63b2a195d8b415fa01df1947fdecad9
work_keys_str_mv	AT codrutaignea overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT anastasiaathanasakoglou overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT aggelikiandreadelli overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT mariaapostolaki overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT minasiakovides overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT euripidesgstephanou overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT antoniosmmakris overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast AT sotiriosckampranis overcomingtheplasticityofplantspecializedmetabolismforselectivediterpeneproductioninyeast
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Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast

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