Coenzyme A biosynthesis in Bacillus subtilis : discovery of a novel precursor metabolite for salvage and its uptake system Article Swipe
Robert Warneke
,
Christina Herzberg
,
Moritz Klein
,
Christoph Elfmann
,
J. Dittmann
,
Kirstin Feussner
,
Ivo Feußner
,
Jörg Stülke
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.01772-24
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.01772-24
The Gram-positive model bacterium Bacillus subtilis is used for many biotechnological applications, including the large-scale production of vitamins. For vitamin B5, a precursor for coenzyme A synthesis, there is so far no established fermentation process available, and the metabolic pathways that involve this vitamin are only partially understood. In this study, we have elucidated the complete pathways for the biosynthesis of pantothenate and coenzyme A in B. subtilis . Pantothenate can not only be synthesized but also be taken up from the medium. We have identified the enzymes and the transporter involved in the pantothenate biosynthesis and uptake. High-affinity vitamin B5 uptake in B. subtilis requires an ATP-driven energy coupling factor transporter with PanU (previously YhfU) as the substrate-specific subunit. Moreover, we have identified a salvage pathway for coenzyme A acquisition that acts on complex medium even in the absence of pantothenate synthesis. This pathway requires rewiring of sulfur metabolism resulting in the increased expression of a cysteine transporter. In the salvage pathway, the bacteria import cysteinopantetheine, a novel naturally occurring metabolite, using the cystine transport system TcyJKLMN. This work lays the foundation for the development of effective processes for vitamin B5 and coenzyme A production using B. subtilis . IMPORTANCE Vitamins are essential components of the diet of animals and humans. Vitamins are thus important targets for biotechnological production. While efficient fermentation processes have been developed for several vitamins, this is not the case for vitamin B5 (pantothenate), the precursor of coenzyme A. We have elucidated the complete pathway for coenzyme A biosynthesis in the biotechnological workhorse Bacillus subtilis . Moreover, a salvage pathway for coenzyme A synthesis was found in this study. Normally, this pathway depends on pantetheine; however, we observed activity of the salvage pathway on complex medium in mutants lacking the pantothenate biosynthesis pathway even in the absence of supplemented pantetheine. This required rewiring of metabolism by expressing a cystine transporter due to acquisition of mutations affecting the regulation of cysteine metabolism. This shows how the hidden “underground metabolism” can give rise to the rapid formation of novel metabolic pathways.
Related Topics
Concepts
Bacillus subtilis
Biochemistry
Biosynthesis
Coenzyme A
Metabolic engineering
Cofactor
Nucleotide salvage
Metabolic pathway
Chemistry
Biology
Enzyme
Bacteria
Nucleotide
Reductase
Gene
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/mbio.01772-24
- OA Status
- gold
- Cited By
- 9
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4401978476
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4401978476Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1128/mbio.01772-24Digital Object Identifier
- Title
-
Coenzyme A biosynthesis in Bacillus subtilis : discovery of a novel precursor metabolite for salvage and its uptake systemWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-08-28Full publication date if available
- Authors
-
Robert Warneke, Christina Herzberg, Moritz Klein, Christoph Elfmann, J. Dittmann, Kirstin Feussner, Ivo Feußner, Jörg StülkeList of authors in order
- Landing page
-
https://doi.org/10.1128/mbio.01772-24Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1128/mbio.01772-24Direct OA link when available
- Concepts
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Bacillus subtilis, Biochemistry, Biosynthesis, Coenzyme A, Metabolic engineering, Cofactor, Nucleotide salvage, Metabolic pathway, Chemistry, Biology, Enzyme, Bacteria, Nucleotide, Reductase, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 8, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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57Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Vitamins | 202, 213 |
| abstract_inverted_index.activity | 284 |
| abstract_inverted_index.bacteria | 165 |
| abstract_inverted_index.coenzyme | 25, 64, 129, 194, 243, 252, 267 |
| abstract_inverted_index.complete | 56, 249 |
| abstract_inverted_index.coupling | 110 |
| abstract_inverted_index.cysteine | 158, 325 |
| abstract_inverted_index.however, | 281 |
| abstract_inverted_index.involved | 92 |
| abstract_inverted_index.observed | 283 |
| abstract_inverted_index.pathway, | 163 |
| abstract_inverted_index.pathways | 40, 57 |
| abstract_inverted_index.required | 307 |
| abstract_inverted_index.requires | 106, 146 |
| abstract_inverted_index.rewiring | 147, 308 |
| abstract_inverted_index.subtilis | 6, 68, 105, 199, 260 |
| abstract_inverted_index.subunit. | 120 |
| abstract_inverted_index.Moreover, | 121, 262 |
| abstract_inverted_index.Normally, | 275 |
| abstract_inverted_index.TcyJKLMN. | 178 |
| abstract_inverted_index.affecting | 321 |
| abstract_inverted_index.bacterium | 4 |
| abstract_inverted_index.developed | 227 |
| abstract_inverted_index.effective | 188 |
| abstract_inverted_index.efficient | 222 |
| abstract_inverted_index.essential | 204 |
| abstract_inverted_index.formation | 340 |
| abstract_inverted_index.important | 216 |
| abstract_inverted_index.including | 13 |
| abstract_inverted_index.increased | 154 |
| abstract_inverted_index.metabolic | 39, 343 |
| abstract_inverted_index.mutations | 320 |
| abstract_inverted_index.naturally | 170 |
| abstract_inverted_index.occurring | 171 |
| abstract_inverted_index.partially | 47 |
| abstract_inverted_index.pathways. | 344 |
| abstract_inverted_index.precursor | 23, 241 |
| abstract_inverted_index.processes | 189, 224 |
| abstract_inverted_index.resulting | 151 |
| abstract_inverted_index.synthesis | 269 |
| abstract_inverted_index.transport | 176 |
| abstract_inverted_index.vitamins, | 230 |
| abstract_inverted_index.vitamins. | 18 |
| abstract_inverted_index.workhorse | 258 |
| abstract_inverted_index.ATP-driven | 108 |
| abstract_inverted_index.IMPORTANCE | 201 |
| abstract_inverted_index.available, | 36 |
| abstract_inverted_index.components | 205 |
| abstract_inverted_index.elucidated | 54, 247 |
| abstract_inverted_index.expressing | 312 |
| abstract_inverted_index.expression | 155 |
| abstract_inverted_index.foundation | 183 |
| abstract_inverted_index.identified | 86, 124 |
| abstract_inverted_index.metabolism | 150, 310 |
| abstract_inverted_index.production | 16, 196 |
| abstract_inverted_index.regulation | 323 |
| abstract_inverted_index.synthesis, | 27 |
| abstract_inverted_index.synthesis. | 143 |
| abstract_inverted_index.(previously | 115 |
| abstract_inverted_index.acquisition | 131, 318 |
| abstract_inverted_index.development | 186 |
| abstract_inverted_index.established | 33 |
| abstract_inverted_index.large-scale | 15 |
| abstract_inverted_index.metabolism. | 326 |
| abstract_inverted_index.metabolite, | 172 |
| abstract_inverted_index.production. | 220 |
| abstract_inverted_index.synthesized | 75 |
| abstract_inverted_index.transporter | 91, 112, 315 |
| abstract_inverted_index.understood. | 48 |
| abstract_inverted_index.Pantothenate | 70 |
| abstract_inverted_index.biosynthesis | 60, 96, 254, 297 |
| abstract_inverted_index.fermentation | 34, 223 |
| abstract_inverted_index.pantetheine. | 305 |
| abstract_inverted_index.pantetheine; | 280 |
| abstract_inverted_index.pantothenate | 62, 95, 142, 296 |
| abstract_inverted_index.supplemented | 304 |
| abstract_inverted_index.transporter. | 159 |
| abstract_inverted_index.Gram-positive | 2 |
| abstract_inverted_index.High-affinity | 99 |
| abstract_inverted_index.applications, | 12 |
| abstract_inverted_index.metabolism” | 333 |
| abstract_inverted_index.“underground | 332 |
| abstract_inverted_index.(pantothenate), | 239 |
| abstract_inverted_index.biotechnological | 11, 219, 257 |
| abstract_inverted_index.substrate-specific | 119 |
| abstract_inverted_index.cysteinopantetheine, | 167 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 90 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 8 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/7 |
| sustainable_development_goals[0].score | 0.4399999976158142 |
| sustainable_development_goals[0].display_name | Affordable and clean energy |
| citation_normalized_percentile.value | 0.91706319 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |