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Title: Two-step pathway for isoprenoid synthesis

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America

Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.

Research Organization:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Sponsoring Organization:
USDOE Office of Energy Efficiency and Renewable Energy (EERE)
Grant/Contract Number:
EE0007531; SC0008744
OSTI ID:
1488765
Alternate ID(s):
OSTI ID: 1613431
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 116 Journal Issue: 2; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 131 works
Citation information provided by
Web of Science

References (32)

High-Level Production of the Industrial Product Lycopene by the Photosynthetic Bacterium Rhodospirillum rubrum journal August 2012
The Standard European Vector Architecture (SEVA): a coherent platform for the analysis and deployment of complex prokaryotic phenotypes journal November 2012
Identification in Haloferax volcanii of Phosphomevalonate Decarboxylase and Isopentenyl Phosphate Kinase as Catalysts of the Terminal Enzyme Reactions in an Archaeal Alternate Mevalonate Pathway journal December 2013
Carotenoid Biosynthesis in the Primitive Red Alga Cyanidioschyzon merolae journal November 2006
Combination of Entner-Doudoroff Pathway with MEP Increases Isoprene Production in Engineered Escherichia coli journal December 2013
Detergent-solubilization, purification, and characterization of membrane-bound 3-hydroxy-3-methylglutaryl-coenzyme A reductase from radish seedlings journal January 1986
Multigene Editing in the Escherichia coli Genome via the CRISPR-Cas9 System journal January 2015
Optimization of a heterologous pathway for the production of flavonoids from glucose journal July 2011
Lycopene; chemistry, biosynthesis, metabolism and degradation under various abiotic parameters journal January 2013
Current development in isoprenoid precursor biosynthesis and regulation journal August 2013
Properties of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase from Pisum sativum seedlings journal April 1975
Feedback Inhibition of Deoxy-d-xylulose-5-phosphate Synthase Regulates the Methylerythritol 4-Phosphate Pathway journal April 2013
Microbial production of isoprenoids journal September 2011
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids journal June 2003
Characterization of a Feedback-Resistant Mevalonate Kinase from the Archaeon Methanosarcina mazei journal September 2011
Designing a New Entry Point into Isoprenoid Metabolism by Exploiting Fructose-6-Phosphate Aldolase Side Reactivity of Escherichia coli journal April 2017
High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli journal February 2009
BglBrick vectors and datasheets: A synthetic biology platform for gene expression journal January 2011
Metabolite Profiling Identified Methylerythritol Cyclodiphosphate Efflux as a Limiting Step in Microbial Isoprenoid Production journal November 2012
Improving the catalytic activity of isopentenyl phosphate kinase through protein coevolution analysis journal April 2016
Preparation of Lycopene from Tomato Paste for Use as Spectrophotometric Standard journal October 1949
Mechanistic Insights into Taxadiene Epoxidation by Taxadiene-5α-Hydroxylase journal December 2015
Design, construction and characterization of a set of insulated bacterial promoters journal September 2010
Biosynthesis of Plant Isoprenoids: Perspectives for Microbial Engineering journal June 2009
Discovery of a metabolic alternative to the classical mevalonate pathway journal December 2013
Brassica juncea 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase 1: expression and characterization of recombinant wild-type and mutant enzymes journal October 2004
Characterization and Thermal Isomerization of ( all - E )-Lycopene journal December 2013
Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production journal March 2016
Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli journal September 2010
Plant volatile terpenoid metabolism: Biosynthetic genes, transcriptional regulation and subcellular compartmentation journal May 2010
Substrate Promiscuity of N-Acetylhexosamine 1-Kinases journal July 2011
Substrate promiscuity of pyruvate kinase on various deoxynucleoside diphosphates for synthesis of deoxynucleoside triphosphates journal November 2008

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