Adaptation to perturbation of metabolism

Complex bacteria like the Gram-negative and Gram-positive model organisms Escherichia coli and Bacillus subtilis, respectively, have versatile metabolic properties allowing them to thrive in a variety of niches. Due to their metabolic adaptability, these bacteria are also often used for biotechnological applications. The enzyme equipment of a cell largely determines its metabolic properties. E.g., a bacterium is only capable of growing with a certain sugar as the sole source of carbon if the cells possess a transport system and enzymes for energy conversion and for generating essential building blocks, which are required to build up a cell. Therefore, the emergence of catabolic and anabolic routes is a crucial step for the development and evolution of complex cellular systems. However, the so-called underground metabolism or side activities of prevalent metabolic enzymes enable the bacteria to make use of native and non-native enzymes for metabolic rewiring. We are interested in how bacteria can circumvent metabolic lesions through mutations and bypasses.

 

Why are we interested in genomic adaptation to perturbation of metabolism?

  • In many cases, genetic lesions can be bypassed by a few genomic alterations.
  • The characterization of genetically adapted bacteria (suppressors) often unmasks promiscuous enzymes.
  • Suppressor analyses facilitate the functional characterization of proteins.

 

Publications

Mardoukhi MSY, Rapp J, Irisarri I, Gunka K, Link H, Marienhagen J, de Vries J, Stülke J, Commichau FM (2024) Metabolic rewiring enables ammonium assimilation via a non-canonical fumarate-based pathway. Microb Biotechnol. 17: e14429.

Stecker D, Hoffmann T, Link H, Commichau FM, Bremer E (2022) L-Proline synthesis mutants of Bacillus subtilis overcome osmotic sensitivity by genetically adapting L-arginine metabolism. Front Microbiol. 13: 908304.

Richts B Lentes S Poehlein A Daniel R Commichau FM (2021) A Bacillus subtilis pdxT mutant suppresses vitamin B6 limitation by acquiring mutations enhancing pdxS gene dosage and ammonium assimilation. Environ Microbiol Rep. 13: 218-233.

Richts B, Commichau FM (2021) Underground metabolism facilitates the evolution of novel pathways for vitamin B6 biosynthesis. Appl Microbiol Biotechnol. 105: 2297-2305.

Acevedo-Rocha CG Gronenberg LS Mack M Commichau FM Genee HJ (2019) Microbial cell factories for the sustainable manufacturing of B vitamins. Curr Opin Biotechnol 56: 18-29.

Richts B Rosenberg J Commichau FM (2019) A survey of pyridoxal 5′-phosphate-dependent proteins in the Gram-positive model bacterium Bacillus subtilis. Front Mol Biosci 6: 32.

Rosenberg J Commichau FM (2019) Harnessing underground metabolism for pathway development. Trends Biotechnol 37: 29-37.

Rosenberg J Yeak KC Commichau FM (2018) A two-step evolutionary process establishes a non-native vitamin B6 pathway in Bacillus subtilis. Environ Microbiol 20: 156-168.

Dormeyer M Lentes S Ballin P Wilkens M Klumpp S Kohlheyer D Stannek L Grünberger A Commichau FM (2018) Visualization of tandem repeat mutagenesis in Bacillus subtilis. DNA Repair (Amst) 63: 10-15.

Rosenberg J Ischebeck T Commichau FM (2017) Vitamin B6 metabolism in microbes and approaches for fermentative production. Biotechnol Adv 35: 31-40.

Dormeyer M Lübke AL Müller P Lentes S Reuß DR Thürmer A Stülke J Daniel R Brantl S Commichau FM (2017) Hierarchical mutational events compensate for glutamate auxotrophy of a Bacillus subtilis gltC mutant. Environ Microbiol Rep 9: 279-289.

Rosenberg J Müller P Lentes S Thiele MJ Zeigler DR Tödter D Paulus H Brantl S Stülke J Commichau FM (2016) ThrR, a DNA-binding transcription factor involved in controlling threonine biosynthesis in Bacillus subtilis. Mol Microbiol 101: 879-893.

Dormeyer M Egelkamp R Thiele MJ Hammer E Gunka K Stannek L Völker U Commichau FM (2015) A novel engineering tool in the Bacillus subtilis toolbox: inducer-free activation of gene expression by selection-driven promoter decryptification. Microbiology 161: 354-61. 

Commichau FM Alzinger A Sande R Bretzel W Reuß DR Dormeyer M Chevreux B Schuldes J Daniel R Akeroyd M Wyss M Hohmann H Prágai Z (2015) Engineering Bacillus subtilis for the conversion of the antimetabolite 4-hydroxy-L-threonine to pyridoxine. Metab Eng 29: 196-207.

Commichau FM Alzinger A Sande R Bretzel W Meyer FM Chevreux B Wyss M Hohmann H Prágai Z (2014) Overexpression of a non-native deoxyxylulose-dependent vitamin B6 pathway in Bacillus subtilis for the production of pyridoxine. Metab Eng 25: 38-49.

Gunka K Stannek L Care R Commichau FM (2013) Selection-driven accumulation of suppressor mutants in Bacillus subtilis: the apparent high mutation frequency of the cryptic gudB gene and the rapid clonal expansion of gudB+ suppressors are due to growth under selection. PLoS One 8: e66120. 

Gunka K Tholen S Gerwig J Herzberg C Stüke J Commichau FM (2012) A high-frequency mutation in Bacillus subtilis: requirements for the decryptification of the gudB glutamate dehydrogenase gene. J Bacteriol 196: 1036-1044.