BER launches Environmental System Science Program. Visit our new website under construction!

U.S. Department of Energy Office of Biological and Environmental Research

BER Research Highlights


Phenolic Amides are Potent Inhibitors of de novo Nucleotide Biosynthesis
Published: June 12, 2015
Posted: September 01, 2015

Lignocellulose-derived hydrolysates contain several different inhibitors (collectively called lignotoxins or LTs) that arise during pretreatment of biomass. Determining the mechanisms by which yeast or bacteria are adversely affected by LTs is a key step toward improving the efficiency of fermentation and bioconversion. Prior work has established that LTs present in ammonia pretreated corn stover hydrolysates inhibit growth and sugar utilization in Escherichia coli. Researchers at the Department of Energy’s Great Lakes Bioenergy Research Center (GLBRC) have now keyed in on two phenolic amine LTs, feruloyl amide (FA) and coumaroyl amide (CA). These inhibitors are important because these two alone are sufficient to recapitulate the inhibitory effects of all LTs present. Analysis of the metabolome in untreated versus treated cells indicated that these phenolic amides cause rapid accumulation of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis. Moreover, isotopic tracer studies confirmed that carbon and nitrogen flux into nucleotides is inhibited by the amides, suggesting that these phenolic amines are potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Biochemical studies showed that the amides directly inhibit glutamine amidotransferases, with FA acting as a competitive inhibitor of the E. coli enzyme responsible for the first committed step in de novo purine biosynthesis. Supplementation of cultures with nucleosides was sufficient to reverse the effect of the amides, suggesting the ability to bypass the block in de novo nucleotide biosynthesis via salvage pathways. Collectively, these results provide a direct mechanism for the inhibitory effects of phenolic amides, knowledge that will inform future design of biocatalysts for improved bioconversion.

Reference: Pisithkul, T., T. B. Jacobson, T. J. O'Brien, D. M. Stevenson, and D. Amador-Noguez. 2015. “Phenolic Amides are Potent Inhibitors of De Novo Nucleotide Biosynthesis,” Applied and Environmental Microbiology 81(17), 5761-72. DOI: 10.1128/AEM.01324-15. (Reference link)

Contact: Kent Peters, SC-23.2, (301) 903-5549
Topic Areas:

  • Research Area: Genomic Analysis and Systems Biology
  • Research Area: Microbes and Communities
  • Research Area: Plant Systems and Feedstocks, Plant-Microbe Interactions
  • Research Area: Sustainable Biofuels and Bioproducts
  • Research Area: DOE Bioenergy Research Centers (BRC)

Division: SC-33.2 Biological Systems Science Division, BER

 

BER supports basic research and scientific user facilities to advance DOE missions in energy and environment. More about BER

Recent Highlights

Mar 23, 2021
Molecular Connections from Plants to Fungi to Ants
Lipids transfer energy and serve as an inter-kingdom communication tool in leaf-cutter ants&rsqu [more...]

Mar 19, 2021
Microbes Use Ancient Metabolism to Cycle Phosphorus
Microbial cycling of phosphorus through reduction-oxidation reactions is older and more widespre [more...]

Feb 22, 2021
Warming Soil Means Stronger Microbe Networks
Soil warming leads to more complex, larger, and more connected networks of microbes in those soi [more...]

Jan 27, 2021
Labeling the Thale Cress Metabolites
New data pipeline identifies metabolites following heavy isotope labeling.

Analysis [more...]

Aug 31, 2020
Novel Bacterial Clade Reveals Origin of Form I Rubisco
Objectives

  • All plant biomass is sourced from the carbon-fixing enzyme Rub [more...]

List all highlights (possible long download time)