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Bacillus megaterium—from simple soil bacterium to industrial protein production host

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Abstract

Bacillus megaterium has been industrially employed for more than 50 years, as it possesses some very useful and unusual enzymes and a high capacity for the production of exoenzymes. It is also a desirable cloning host for the production of intact proteins, as it does not possess external alkaline proteases and can stably maintain a variety of plasmid vectors. Genetic tools for this species include transducing phages and several hundred mutants covering the processes of biosynthesis, catabolism, division, sporulation, germination, antibiotic resistance, and recombination. The seven plasmids of B. megaterium strain QM B1551 contain several unusual metabolic genes that may be useful in bioremediation. Recently, several recombinant shuttle vectors carrying different strong inducible promoters and various combinations of affinity tags for simple protein purification have been constructed. Leader sequences-mediated export of affinity-tagged proteins into the growth medium was made possible. These plasmids are commercially available. For a broader application of B. megaterium in industry, sporulation and protease-deficient as well as UV-sensitive mutants were constructed. The genome sequence of two different strains, plasmidless DSM319 and QM B1551 carrying seven natural plasmids, is now available. These sequences allow for a systems biotechnology optimization of the production host B. megaterium. Altogether, a “toolbox” of hundreds of genetically characterized strains, genetic methods, vectors, hosts, and genomic sequences make B. megaterium an ideal organism for industrial, environmental, and experimental applications.

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Acknowledgments

This work was supported in part by grant IR15 GM64447-01A1 from the National Institutes of Health (PV), a gift from Abbott Laboratories, by the Deutsche Forschungsgemeinschaft (SFB 578) and Fonts der chemischen Industrie (RB, TF, WDD, DJ), and by grants from the German Ministry of Research and Education (BMBF) Grant Nos. 0312613 and 0313645 (FM). It represents the work of many graduate and undergraduate students in the Vary’s laboratory to whom she is most grateful. TF would like to thank the Structure Biology Department of the Helmholtz Zentrum für Infektionsforschung (HZI) Braunschweig, especially Dr. Manfred Nimtz and Claudia Hanko, for their support in GC/MS analysis. A number of students and coworkers received their Diploma or doctoral degrees during this period of time; their contribution is gratefully acknowledged (FM, WDD, DJ).

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Vary, P.S., Biedendieck, R., Fuerch, T. et al. Bacillus megaterium—from simple soil bacterium to industrial protein production host. Appl Microbiol Biotechnol 76, 957–967 (2007). https://doi.org/10.1007/s00253-007-1089-3

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