Cytochrome P450–catalyzed biosynthesis of furanoditerpenoids in the bioenergy crop switchgrass (Panicum virgatum L.)
Abstract
Specialized diterpenoid metabolites are important mediators of plant-environment interactions in monocot crops. To understand metabolite functions in plant environmental adaptation that ultimately can enable crop improvement strategies, a deeper knowledge of the underlying species-specific biosynthetic pathways is required. Furthermore, we report the genomics-enabled discovery of five cytochrome P450 monooxygenases (CYP71Z25-CYP71Z29) that form previously unknown furanoditerpenoids in the monocot bioenergy crop Panicum virgatum (switchgrass). Combinatorial pathway reconstruction showed that CYP71Z25-CYP71Z29 catalyze furan ring addition directly to primary diterpene alcohol intermediates derived from distinct class II diterpene synthase products. Transcriptional co-expression patterns and the presence of select diterpenoids in switchgrass roots support the occurrence of P450-derived furanoditerpenoids in planta. Integrating molecular dynamics, structural analysis and targeted mutagenesis identified active site determinants that contribute to the distinct catalytic specificities underlying the broad substrate promiscuity of CYP71Z25-CYP71Z29 for native and non-native diterpenoids.
- Authors:
-
[1]
- Univ. of California, Davis, CA (United States)
- Hudson Alpha Inst. for Biotechnology, Huntsville, AL (United States)
- Publication Date:
- Research Org.:
- Univ. of California, Davis, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1828388
- Grant/Contract Number:
- SC0019178; AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- The Plant Journal
- Additional Journal Information:
- Journal Volume: 108; Journal Issue: 4; Journal ID: ISSN 0960-7412
- Publisher:
- Society for Experimental Biology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Panicum virgatum; cytochrome P450 monooxygenase; diterpenoid biosynthesis; plant natural products; plant specialized metabolism
Citation Formats
Muchlinski, Andrew, Jia, Meirong, Tiedge, Kira, Fell, Jason S., Pelot, Kyle A., Chew, Lisl, Davisson, Danielle, Chen, Yuxuan, Siegel, Justin, Lovell, John T., and Zerbe, Philipp. Cytochrome P450–catalyzed biosynthesis of furanoditerpenoids in the bioenergy crop switchgrass (Panicum virgatum L.). United States: N. p., 2021.
Web. doi:10.1111/tpj.15492.
Muchlinski, Andrew, Jia, Meirong, Tiedge, Kira, Fell, Jason S., Pelot, Kyle A., Chew, Lisl, Davisson, Danielle, Chen, Yuxuan, Siegel, Justin, Lovell, John T., & Zerbe, Philipp. Cytochrome P450–catalyzed biosynthesis of furanoditerpenoids in the bioenergy crop switchgrass (Panicum virgatum L.). United States. https://doi.org/10.1111/tpj.15492
Muchlinski, Andrew, Jia, Meirong, Tiedge, Kira, Fell, Jason S., Pelot, Kyle A., Chew, Lisl, Davisson, Danielle, Chen, Yuxuan, Siegel, Justin, Lovell, John T., and Zerbe, Philipp. Mon .
"Cytochrome P450–catalyzed biosynthesis of furanoditerpenoids in the bioenergy crop switchgrass (Panicum virgatum L.)". United States. https://doi.org/10.1111/tpj.15492. https://www.osti.gov/servlets/purl/1828388.
@article{osti_1828388,
title = {Cytochrome P450–catalyzed biosynthesis of furanoditerpenoids in the bioenergy crop switchgrass (Panicum virgatum L.)},
author = {Muchlinski, Andrew and Jia, Meirong and Tiedge, Kira and Fell, Jason S. and Pelot, Kyle A. and Chew, Lisl and Davisson, Danielle and Chen, Yuxuan and Siegel, Justin and Lovell, John T. and Zerbe, Philipp},
abstractNote = {Specialized diterpenoid metabolites are important mediators of plant-environment interactions in monocot crops. To understand metabolite functions in plant environmental adaptation that ultimately can enable crop improvement strategies, a deeper knowledge of the underlying species-specific biosynthetic pathways is required. Furthermore, we report the genomics-enabled discovery of five cytochrome P450 monooxygenases (CYP71Z25-CYP71Z29) that form previously unknown furanoditerpenoids in the monocot bioenergy crop Panicum virgatum (switchgrass). Combinatorial pathway reconstruction showed that CYP71Z25-CYP71Z29 catalyze furan ring addition directly to primary diterpene alcohol intermediates derived from distinct class II diterpene synthase products. Transcriptional co-expression patterns and the presence of select diterpenoids in switchgrass roots support the occurrence of P450-derived furanoditerpenoids in planta. Integrating molecular dynamics, structural analysis and targeted mutagenesis identified active site determinants that contribute to the distinct catalytic specificities underlying the broad substrate promiscuity of CYP71Z25-CYP71Z29 for native and non-native diterpenoids.},
doi = {10.1111/tpj.15492},
journal = {The Plant Journal},
number = 4,
volume = 108,
place = {United States},
year = {Mon Sep 13 00:00:00 EDT 2021},
month = {Mon Sep 13 00:00:00 EDT 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
CYP76M7 Is an ent -Cassadiene C11α-Hydroxylase Defining a Second Multifunctional Diterpenoid Biosynthetic Gene Cluster in Rice
journal, October 2009
- Swaminathan, Sivakumar; Morrone, Dana; Wang, Qiang
- The Plant Cell, Vol. 21, Issue 10
A Modular Approach for Facile Biosynthesis of Labdane-Related Diterpenes
journal, May 2007
- Cyr, Anthony; Wilderman, P. Ross; Determan, Mara
- Journal of the American Chemical Society, Vol. 129, Issue 21
A Novel Labda-7,13E-dien-15-ol-Producing Bifunctional Diterpene Synthase from Selaginella moellendorffii
journal, July 2011
- Mafu, Sibongile; Hillwig, Matthew L.; Peters, Reuben J.
- ChemBioChem, Vol. 12, Issue 13
Transcriptomic analysis of UV-treated rice leaves reveals UV-induced phytoalexin biosynthetic pathways and their regulatory networks in rice
journal, December 2013
- Park, Hye Lin; Lee, Sang-Won; Jung, Ki-Hong
- Phytochemistry, Vol. 96
Bifunctional Abietadiene Synthase: Free Diffusive Transfer of the (+)-Copalyl Diphosphate Intermediate between Two Distinct Active Sites
journal, September 2001
- Peters, Reuben J.; Ravn, Matthew M.; Coates, Robert M.
- Journal of the American Chemical Society, Vol. 123, Issue 37
Identification of UV-Induced Diterpenes Including a New Diterpene Phytoalexin, Phytocassane F, from Rice Leaves by Complementary GC/MS and LC/MS Approaches
journal, April 2015
- Horie, Kiyotaka; Inoue, Yasuno; Sakai, Miki
- Journal of Agricultural and Food Chemistry, Vol. 63, Issue 16
New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0
journal, March 2010
- Guindon, Stéphane; Dufayard, Jean-François; Lefort, Vincent
- Systematic Biology, Vol. 59, Issue 3
Functional characterization of the rice kaurene synthase-like gene family
journal, February 2007
- Xu, Meimei; Ross Wilderman, P.; Morrone, Dana
- Phytochemistry, Vol. 68, Issue 3
Demonstration That Menthofuran Synthase of Mint (Mentha) Is a Cytochrome P450 Monooxygenase: Cloning, Functional Expression, and Characterization of the Responsible Gene
journal, June 2001
- Bertea, Cinzia M.; Schalk, Michel; Karp, Frank
- Archives of Biochemistry and Biophysics, Vol. 390, Issue 2
High-Resolution Comparative Modeling with RosettaCM
journal, October 2013
- Song, Yifan; DiMaio, Frank; Wang, Ray Yu-Ruei
- Structure, Vol. 21, Issue 10
RosettaLigand Docking with Full Ligand and Receptor Flexibility
journal, January 2009
- Davis, Ian W.; Baker, David
- Journal of Molecular Biology, Vol. 385, Issue 2
Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass
journal, January 2021
- Lovell, John T.; MacQueen, Alice H.; Mamidi, Sujan
- Nature, Vol. 590, Issue 7846
Increasing diterpene yield with a modular metabolic engineering system in E. coli: comparison of MEV and MEP isoprenoid precursor pathway engineering
journal, September 2009
- Morrone, Dana; Lowry, Luke; Determan, Mara K.
- Applied Microbiology and Biotechnology, Vol. 85, Issue 6
The Application of Synthetic Biology to Elucidation of Plant Mono-, Sesqui-, and Diterpenoid Metabolism
journal, January 2015
- Kitaoka, Naoki; Lu, Xuan; Yang, Bing
- Molecular Plant, Vol. 8, Issue 1
Parsing a multifunctional biosynthetic gene cluster from rice: Biochemical characterization of CYP71Z6 & 7
journal, October 2011
- Wu, Yisheng; Hillwig, Matthew L.; Wang, Qiang
- FEBS Letters, Vol. 585, Issue 21
Biosynthesis and Emission of Stress-Induced Volatile Terpenes in Roots and Leaves of Switchgrass (Panicum virgatum L.)
journal, September 2019
- Muchlinski, Andrew; Chen, Xinlu; Lovell, John T.
- Frontiers in Plant Science, Vol. 10
Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase
journal, February 2017
- Pelot, Kyle A.; Mitchell, Rod; Kwon, Moonhyuk
- The Plant Journal, Vol. 89, Issue 5
The Maize An2 Gene is Induced by Fusarium Attack and Encodes an ent-Copalyl Diphosphate Synthase
journal, December 2005
- Harris, L. J.; Saparno, A.; Johnston, A.
- Plant Molecular Biology, Vol. 59, Issue 6
A (conditional) role for labdane‐related diterpenoid natural products in rice stomatal closure
journal, February 2021
- Zhang, Juan; Li, Riqing; Xu, Meimei
- New Phytologist, Vol. 230, Issue 2
Assessment of drought tolerance of 49 switchgrass (Panicum virgatum) genotypes using physiological and morphological parameters
journal, September 2015
- Liu, Yiming; Zhang, Xunzhong; Tran, Hong
- Biotechnology for Biofuels, Vol. 8, Issue 1
Biosynthesis and Biological Functions of Terpenoids in Plants
book, January 2015
- Tholl, Dorothea
- Biotechnology of Isoprenoids
Characterization of CYP71Z18 indicates a role in maize zealexin biosynthesis
journal, January 2016
- Mao, Hongjie; Liu, Jiang; Ren, Fei
- Phytochemistry, Vol. 121
ROSETTALIGAND: Protein-small molecule docking with full side-chain flexibility
journal, November 2006
- Meiler, Jens; Baker, David
- Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3
Net energy of cellulosic ethanol from switchgrass
journal, January 2008
- Schmer, M. R.; Vogel, K. P.; Mitchell, R. B.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 2
The next green movement: Plant biology for the environment and sustainability
journal, September 2016
- Jez, J. M.; Lee, S. G.; Sherp, A. M.
- Science, Vol. 353, Issue 6305
Optimization of recombinant expression enables discovery of novel cytochrome P450 activity in rice diterpenoid biosynthesis
journal, March 2015
- Kitaoka, Naoki; Wu, Yisheng; Xu, Meimei
- Applied Microbiology and Biotechnology, Vol. 99, Issue 18
Genetic strategies for improving crop yields
journal, November 2019
- Bailey-Serres, Julia; Parker, Jane E.; Ainsworth, Elizabeth A.
- Nature, Vol. 575, Issue 7781
Evolution of substrate recognition sites (SRSs) in cytochromes P450 from Apiaceae exemplified by the CYP71AJ subfamily
journal, June 2015
- Dueholm, Bjørn; Krieger, Célia; Drew, Damian
- BMC Evolutionary Biology, Vol. 15, Issue 1
Integrating transcriptional, metabolomic, and physiological responses to drought stress and recovery in switchgrass (Panicum virgatum L.)
journal, January 2014
- Meyer, Eli; Aspinwall, Michael J.; Lowry, David B.
- BMC Genomics, Vol. 15, Issue 1
A Pareto-Optimal Refinement Method for Protein Design Scaffolds
journal, April 2013
- Nivón, Lucas Gregorio; Moretti, Rocco; Baker, David
- PLoS ONE, Vol. 8, Issue 4
Functional Characterization of Two Class II Diterpene Synthases Indicates Additional Specialized Diterpenoid Pathways in Maize (Zea mays)
journal, October 2018
- Murphy, Katherine M.; Ma, Li-Ting; Ding, Yezhang
- Frontiers in Plant Science, Vol. 9
Functional Diversity of Diterpene Synthases in the Biofuel Crop Switchgrass
journal, July 2018
- Pelot, Kyle A.; Chen, Ruibing; Hagelthorn, David M.
- Plant Physiology, Vol. 178, Issue 1
Multiple genes recruited from hormone pathways partition maize diterpenoid defences
journal, September 2019
- Ding, Yezhang; Murphy, Katherine M.; Poretsky, Elly
- Nature Plants, Vol. 5, Issue 10
Accumulation of terpenoid phytoalexins in maize roots is associated with drought tolerance: Maize root phytoalexins play a role in drought tolerance
journal, January 2015
- Vaughan, Martha M.; Christensen, Shawn; Schmelz, Eric A.
- Plant, Cell & Environment, Vol. 38, Issue 11
Macromolecular Modeling with Rosetta
journal, June 2008
- Das, Rhiju; Baker, David
- Annual Review of Biochemistry, Vol. 77, Issue 1
Getting back to the grass roots: harnessing specialized metabolites for improved crop stress resilience
journal, August 2021
- Ding, Yezhang; Northen, Trent R.; Khalil, Ahmed
- Current Opinion in Biotechnology, Vol. 70
The foxtail millet ( Setaria italica ) terpene synthase gene family
journal, May 2020
- Karunanithi, Prema S.; Berrios, David I.; Wang, Sadira
- The Plant Journal, Vol. 103, Issue 2
P450s controlling metabolic bifurcations in plant terpene specialized metabolism
journal, September 2017
- Banerjee, Aparajita; Hamberger, Björn
- Phytochemistry Reviews, Vol. 17, Issue 1
Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity
journal, October 2019
- Karunanithi, Prema S.; Zerbe, Philipp
- Frontiers in Plant Science, Vol. 10
Functional identification of rice syn -copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products
journal, August 2004
- Xu, Meimei; Hillwig, Matthew L.; Prisic, Sladjana
- The Plant Journal, Vol. 39, Issue 3
Genomic innovation for crop improvement
journal, March 2017
- Bevan, Michael W.; Uauy, Cristobal; Wulff, Brande B. H.
- Nature, Vol. 543, Issue 7645
Biosynthesis, elicitation and roles of monocot terpenoid phytoalexins
journal, March 2014
- Schmelz, Eric A.; Huffaker, Alisa; Sims, James W.
- The Plant Journal, Vol. 79, Issue 4
Contribution of isopentenyl phosphate to plant terpenoid metabolism
journal, August 2018
- Henry, Laura K.; Thomas, Suzanne T.; Widhalm, Joshua R.
- Nature Plants, Vol. 4, Issue 9
The global burden of pathogens and pests on major food crops
journal, February 2019
- Savary, Serge; Willocquet, Laetitia; Pethybridge, Sarah Jane
- Nature Ecology & Evolution, Vol. 3, Issue 3
Specialized diterpenoid metabolism in monocot crops: Biosynthesis and chemical diversity
journal, April 2020
- Murphy, Katherine M.; Zerbe, Philipp
- Phytochemistry, Vol. 172
The genomic landscape of molecular responses to natural drought stress in Panicum hallii
journal, December 2018
- Lovell, John T.; Jenkins, Jerry; Lowry, David B.
- Nature Communications, Vol. 9, Issue 1
Reference genome sequence of the model plant Setaria
journal, May 2012
- Bennetzen, Jeffrey L.; Schmutz, Jeremy; Wang, Hao
- Nature Biotechnology, Vol. 30, Issue 6
Incorporation of evolutionary information into Rosetta comparative modeling
journal, June 2011
- Thompson, James; Baker, David
- Proteins: Structure, Function, and Bioinformatics, Vol. 79, Issue 8
Functional characterization of wheat ent-kaurene(-like) synthases indicates continuing evolution of labdane-related diterpenoid metabolism in the cereals
journal, December 2012
- Zhou, Ke; Xu, Meimei; Tiernan, Mollie
- Phytochemistry, Vol. 84
Two rings in them all: The labdane-related diterpenoids
journal, January 2010
- Peters, Reuben J.
- Natural Product Reports, Vol. 27, Issue 11
Functional characterization of wheat copalyl diphosphate synthases sheds light on the early evolution of labdane-related diterpenoid metabolism in the cereals
journal, December 2012
- Wu, Yisheng; Zhou, Ke; Toyomasu, Tomonobu
- Phytochemistry, Vol. 84
Naturally occurring furanoditerpenoids: distribution, chemistry and their pharmacological activities
journal, June 2016
- Bao, Han; Zhang, Qingwen; Ye, Yang
- Phytochemistry Reviews, Vol. 16, Issue 2
Fungal and herbivore elicitation of the novel maize sesquiterpenoid, zealexin A4, is attenuated by elevated CO2
journal, December 2017
- Christensen, Shawn A.; Huffaker, Alisa; Sims, James
- Planta, Vol. 247, Issue 4
To Gibberellins and Beyond! Surveying the Evolution of (Di)Terpenoid Metabolism
journal, April 2014
- Zi, Jiachen; Mafu, Sibongile; Peters, Reuben J.
- Annual Review of Plant Biology, Vol. 65, Issue 1
Navigating complexity to breed disease-resistant crops
journal, November 2017
- Nelson, Rebecca; Wiesner-Hanks, Tyr; Wisser, Randall
- Nature Reviews Genetics, Vol. 19, Issue 1
Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza
journal, January 2021
- Ma, Ying; Cui, Guanghong; Chen, Tong
- Nature Communications, Vol. 12, Issue 1
Discovery, Biosynthesis and Stress-Related Accumulation of Dolabradiene-Derived Defenses in Maize
journal, February 2018
- Mafu, Sibongile; Ding, Yezhang; Murphy, Katherine M.
- Plant Physiology, Vol. 176, Issue 4
Effects of elevated [ CO 2 ] on maize defence against mycotoxigenic F usarium verticillioides
journal, May 2014
- Vaughan, Martha M.; Huffaker, Alisa; Schmelz, Eric A.
- Plant, Cell & Environment, Vol. 37, Issue 12
Exploring diterpene metabolism in non-model species: transcriptome-enabled discovery and functional characterization of labda-7,13 E -dienyl diphosphate synthase from Grindelia robusta
journal, July 2015
- Zerbe, Philipp; Rodriguez, Selina M.; Mafu, Sibongile
- The Plant Journal, Vol. 83, Issue 5
Crystal structure of CYP76AH1 in 4-PI-bound state from Salvia miltiorrhiza
journal, April 2019
- Gu, Mingyue; Wang, Mingzhu; Guo, Juan
- Biochemical and Biophysical Research Communications, Vol. 511, Issue 4