Pharming news: periwinkle-bioreactor
Genetic modification of a well-known garden plant, as a result of which the flowering plant was able to express enzymes-halogenases, allowed researchers from the Massachusetts Institute of Technology to force the plant to carry out biosynthesis of complex natural compounds, including halogenated analogues.
The new development will simplify the production of halogen-containing organic compounds of pharmaceutical importance by synthesizing these compounds with the help of flowering plants, rather than using multi-stage chemical transformations or genetically modified microorganisms.
Weerawat Runguphan and Sarah E. O'Connor have previously performed genetic modification of the Madagascar periwinkle (Catharanthus roseus), giving it the ability to convert halogenated tryptamines into halogenated alkaloids. In a new paper, Rungufan, O'Connor and Xudong Qu report that another genetic modification led to the plant being able to produce tryptamines themselves. Their article Integrating carbon-halogen bond formation into medicinal plant metabolism is published in the electronic version of the journal Nature; a short summary can be read in a note from Chemical & Engineering News (Halogenation In The Garden).
The researchers introduced into the periwinkle genetic system genes responsible for the expression of bacterial enzymes-RebH or PyrH halogenases, which in the presence of RebF reductase promote selective chlorination of tryptophan to position 7 (RebH) or 5 (PyrH). The tryptophandecarboxylase produced by the plant promotes the conversion of chlortryptophan into chlortryptamine, which, entering the system of plant synthesis of alkaloids, condenses with monoterpene secologanin (monoterpene secologanin). In the course of further exchange processes directly in plant tissues, chlorinated alkaloids of various structures are obtained from this intermediate. Genetic modification leading to the expression of the RebH enzyme also allows the production of brominated analogues.
The periwinkle was genetically modified in such a way that it grew "hairy roots", then these roots were transferred to a nutrient medium in which they continued to grow and produce chlorine-containing organic compounds.
In the figure from the additional materials to the article
on the left – the roots of differently modified plants,
on the right – wild-type plants
Bradley S. Moore of the Scripps Institution of Oceanography notes that O'Connor's work represents a significant achievement in the field of biological synthesis of naturally occurring chlorine-derived alkaloids. Although such compounds have already been obtained by biochemical means, much simpler organisms than flowering plants have been genetically modified for it.
In the first half of this year, Moore himself was able for the first time to introduce the gene responsible for the expression of the enzyme fluorinase into the genetic sequence of a marine microorganism and "force" this bacterium to produce a fluorinated derivative of the anti-cancer drug salinosporamide (salinosporamide).
Portal "Eternal youth" http://vechnayamolodost.ru according to the materials ChemPort.Ru11.11.2010