Sorangium cellulosum

Sorangium cellulosum is a soil-dwelling Gram-negative bacterium of the group myxobacteria.[1] It is motile and shows gliding motility. Under stressful conditions this motility, as in other myxobacteria, the cells congregate to form fruiting bodies and differentiate into myxospores. These congregating cells make isolation of pure culture and colony counts on agar medium difficult as the bacterium spread and colonies merge.[2] It has an unusually-large genome of 13,033,779 base pairs, making it the largest bacterial genome sequenced to date by roughly 4 Mb.[3]

Myxobacteria
Scientific classification
Kingdom:
Bacteria
Phylum:
Proteobacteria
Class:
Delta Proteobacteria
Order:
Myxococcales
Genus:
Sorangium
Species:
cellulosum

Ecology

S. cellulosum is found in soils, animal feces, and tree bark.[4] The bacterium is a saprophyte deriving its nutrition from cellulose aerobically. It is a prolific producer of secondary fungicides and bactericides that reduce competition in soil environments.[5] In lab samples, S. cellulosum grows on agar medium only when certain cell densities are plated. Quorum-sensing allows Sorangium to grow in communities sufficiently large to metabolize cellulose.[2]

Secondary compounds

Sorangium produces 50% of all known metabolites produced by myxobacteria.[3] These include compounds that are antifungal, antibacterial, antibiotic resistant, or can even disable mammalian cells. These many compounds have sparked intense mining of its extensive genome in exploration of possible industrial and medical applications. Some of these secondary compounds include:

  • Ambruticin and Jerangolid A - Antifungal agents.
  • Chivosazol - a compound that destroys the actin skeleton of eukaryotic cells. It is effective against both fungal and mammalian cells.[6]
  • Epothilones - Compounds that target microtubule function leading to apoptosis.[7] Some derivatives are used to treat human cancers.
  • Myxochelin A - Antibacterial agent that acts by sequestering iron in the environment.[8]
  • Soraphen A - An agent highly effective against plant-pathogenic fungi. It was extensively researched for agricultural use until it was discovered to be a teratogen.[4]

Industrial fermentation and genetic manipulation of S. cellulosum is challenging. Plasmids have been found to not function in S. cellulosum cells. Reproducible genetic alterations must be made directly into the single circular chromosome. [9]

Clinical use

Metabolites secreted by Sorangium cellulosum known as epothilones have been noted to have antineoplastic activity.[10] This has led to the development of analogs which mimic its activity. One such analog, known as ixabepilone is a U.S. Food and Drug Administration approved chemotherapy agent for the treatment of metastatic breast cancer.[11]

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References
  1. Julien B, Fehd R (2003). "Development of a mariner-based transposon for use in Sorangium cellulosum". Appl Environ Microbiol. 69 (10): 6299–301. doi:10.1128/AEM.69.10.6299-6301.2003. PMC 201241. PMID 14532095.
  2. Reichenbach H.; Hofle, G. (1999). "Myxobacteria as producer of secondary metabolites". In Grabley, S.; Thiericke, R. (eds.). Drug Discovery from Nature. pp. 149–179. ISBN 978-3-540-66947-0.
  3. Schneiker S, et al. (2007). "Complete genome sequence of the myxobacterium Sorangium cellulosum". Nature Biotechnology. 25 (11): 1281–1289. doi:10.1038/nbt1354. PMID 17965706.
  4. Zirkle, R.; Ligon, J.M.; Molnar, I. (2004). "Heterlogous production of the antifungal polyketide antibiotic soraphen A of Sorangium cellulosumvSo ce26 in Streptomyces lividans". Microbiology. 150 (Pt 8): 2761–2774. doi:10.1099/mic.0.27138-0. PMID 15289572.
  5. Pradella, S.; Hans, A.; Sproer, C.; Reichenbach, H.; Gerth, K.; Beyer, S. (2002). "Characterization, genome size and genetic manipulation of the myxobacerium Sorangium cellulosum So ce56". Arch Microbiol. 178 (6): 484–494. doi:10.1007/s00203-002-0479-2. PMID 12420170.
  6. Perlova, Olena; Klaus Gerth; Olaf Kaiser; Astrid Hans; Rolf Müller (24 January 2006). "Identification and analysis of the chivosazol biosynthetic gene cluster from the myxobacterial model strain Sorangium cellulosum So ce56". Journal of Biotechnology. 121 (2): 174–191. doi:10.1016/j.jbiotec.2005.10.011. PMID 16313990.
  7. Goodin, Susan; Michael P. Kane; Eric H. Rubin (15 May 2004). "Epothilones: Mechanism of Action and Biologic Activity". Journal of Clinical Oncology. 22 (10): 2015–2025. doi:10.1200/JCO.2004.12.001. PMID 15143095.
  8. Gaitatzis, Nikolaos; Brigitte Kunze; Rolf Muller (25 September 2001). "In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases". Proc Natl Acad Sci U S A. 98 (20): 11136–11141. doi:10.1073/pnas.201167098. PMC 58696. PMID 11562468.
  9. Jaoua, S.; Neff, S.; Schupp, T. (1992). "Transfer of mobilizable plasmids to Sorangium cellulosum and evidence for their integration into the chromosome". Plasmid. 28 (2): 157–165. doi:10.1016/0147-619x(92)90046-d. PMID 1409972.
  10. Lee FY, Borzilleri R, Fairchild CR, et al. (December 2008). "Preclinical discovery of ixabepilone, a highly active antineoplastic agent". Cancer Chemother. Pharmacol. 63 (1): 157–66. doi:10.1007/s00280-008-0724-8. PMID 18347795.
  11. Ixabepilone
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