Rhizoxin is an antimitotic agent with anti-

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

activity. It is isolated from a

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

ic plant

fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from t ...

('' Rhizopus microsporus'') which causes rice seedling blight.

Biosynthesis

Rhizoxin is biosynthesised by ''

Burkholderia ''Burkholderia'' is a genus of Pseudomonadota whose pathogenic members include the ''Burkholderia cepacia'' complex, which attacks humans and ''Burkholderia mallei'', responsible for glanders, a disease that occurs mostly in horses and related ...

rhizoxinica'', a bacterial

endosymbiont An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualistic relationship. (The term endosymbiosis is from the Greek: ἔνδον ''endon'' "within ...

of the fungus ''Rhizopus microsporus''. It is one of a large group of rhizoxin-like compounds produced by the bacteria. The bacterial endosymbiont can be grown independently in culture. This may allow easy harvesting of rhizoxin and the related compounds avoiding total

chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...

, although total chemical synthesis is possible.

Cytotoxic function

Rhizoxin binds beta tubulin in

eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...

cells disrupting microtubule formation. This, in turn, prevents formation of the

mitotic In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...

spindle Spindle may refer to: Textiles and manufacturing * Spindle (textiles), a straight spike to spin fibers into yarn * Spindle (tool), a rotating axis of a machine tool Biology * Common spindle and other species of shrubs and trees in genus ''Euony ...

inhibiting cell division. Additionally rhizoxin can depolymerise assembled microtubules.Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987) The function of rhizoxin is similar to ''Vinca'' alkaloids. Rhizoxin has undergone clinical trials as an anti-cancer drug although it did not reach later stages of

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s due to low activity ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

''. Related compounds to rhizoxin may have improved biological activity.

Structure

Rhizoxin is a 16-membered

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

ring connected to an

oxazole Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak ...

ring by a long unsaturated chain.

References

{{reflist Oxazoles Macrolides Epoxides Polyenes Microtubule inhibitors