Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
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Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast. / Ignea, Codruta; Athanasakoglou, Anastasia; Andreadelli, Aggeliki; Apostolaki, Maria; Iakovides, Minas; Stephanou, Euripides G; Makris, Antonios M; Kampranis, Sotirios.
In: Scientific Reports, Vol. 7, No. 1, 8855, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast
AU - Ignea, Codruta
AU - Athanasakoglou, Anastasia
AU - Andreadelli, Aggeliki
AU - Apostolaki, Maria
AU - Iakovides, Minas
AU - Stephanou, Euripides G
AU - Makris, Antonios M
AU - Kampranis, Sotirios
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41598-017-09592-5
DO - 10.1038/s41598-017-09592-5
M3 - Journal article
C2 - 28821847
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 8855
ER -
ID: 182931626