Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics
Abstract
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:
-
[1];
[2];
[2];
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Environmental Genomics and Systems Biology Division
- Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1416648
- Alternate Identifier(s):
- OSTI ID: 1436660
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- PLoS Genetics
- Additional Journal Information:
- Journal Name: PLoS Genetics Journal Volume: 14 Journal Issue: 1; Journal ID: ISSN 1553-7404
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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., 2018.
Web. https://doi.org/10.1371/journal.pgen.1007147.
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. https://doi.org/10.1371/journal.pgen.1007147
Price, Morgan N., Zane, Grant M., Kuehl, Jennifer V., Melnyk, Ryan A., Wall, Judy D., Deutschbauer, Adam M., and Arkin, Adam P. Thu .
"Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics". United States. https://doi.org/10.1371/journal.pgen.1007147.
@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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