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  • Published Article: Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics

Title: Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics

For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. Here, we studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.
Authors:
ORCiD logo [1] ; ORCiD logo [2] ;  [1] ;  [1] ; ORCiD logo [2] ;  [1] ;  [1]
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  1. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Environmental Genomics and Systems Biology Division
  2. Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Published Article
Journal Name:
PLoS Genetics
Additional Journal Information:
Journal Volume: 14; Journal Issue: 1; Journal ID: ISSN 1553-7404
Publisher:
Public Library of Science
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1416648
Alternate Identifier(s):
OSTI ID: 1436660
Citation Formats
Price, Morgan N., Zane, Grant M., Kuehl, Jennifer V., Melnyk, Ryan A., Wall, Judy D., Deutschbauer, Adam M., and Arkin, Adam P.. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics. United States: N. p., Web. doi:10.1371/journal.pgen.1007147.
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Price, Morgan N., Zane, Grant M., Kuehl, Jennifer V., Melnyk, Ryan A., Wall, Judy D., Deutschbauer, Adam M., & Arkin, Adam P.. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics. United States. doi:10.1371/journal.pgen.1007147.
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Price, Morgan N., Zane, Grant M., Kuehl, Jennifer V., Melnyk, Ryan A., Wall, Judy D., Deutschbauer, Adam M., and Arkin, Adam P.. 2018. "Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics". United States. doi:10.1371/journal.pgen.1007147.
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@article{osti_1416648,
title = {Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics},
author = {Price, Morgan N. and Zane, Grant M. and Kuehl, Jennifer V. and Melnyk, Ryan A. and Wall, Judy D. and Deutschbauer, Adam M. and Arkin, Adam P.},
abstractNote = {For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. Here, we studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.},
doi = {10.1371/journal.pgen.1007147},
journal = {PLoS Genetics},
number = 1,
volume = 14,
place = {United States},
year = {2018},
month = {1}
}
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Works referenced in this record:

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