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Please quote Nature Biotechnology as the source of these items.

The September 2005 issue of Nature Biotechnology is available online.

 September 2005 Previous | Next

Antibiotic assembly line

Nature Biotechnology pp 1171 - 1176

Scientists have turned bacteria into miniature factories for producing novel types of antimicrobial compounds at unprecedented rates, as reported in the September issue of Nature Biotechnology. The ability to rapidly synthesize and identify new antibiotics is particularly important given the emergence of drug-resistant pathogens.

Polyketides, a promising group of chemical compounds with antibacterial, immunosuppressant, antiparasitic and anticancer activity, are naturally synthesized in streptomycete bacteria by large, complex enzymes that function as molecular assembly lines of two-carbon building blocks. Theoretically a simple proposition, the rapid and systematic generation of new types of polyketide-synthesizing enzymes through genetic engineering has until now eluded researchers owing to the inherent complexities of manipulating large stretches of 'functional' DNA sequences from different streptomycete bacteria.

Now, by combining DNA sequences encoding subunits of a particular antibiotic-manufacturing enzyme complex from different microorganisms and expressing them in a single bacterium, Daniel Santi and colleagues were able to 'mix and match' chemical building blocks. These chemical building blocks, which are fused together to make polyketide antibiotics such as erythromycin and amphotericin, are freely combined by the hybrid enzyme complexes to make a diverse range of new compounds with potential antibiotic activity. The ability to rapidly generate these compounds may provide new leads for antibiotics to combat strains of bacteria resistant to current drugs.


Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes pp 1171 - 1176
Hugo G Menzella, Ralph Reid, John R Carney, Sunil S Chandran, Sarah J Reisinger, Kedar G Patel, David A Hopwood & Daniel V Santi
Published online: 14 August 2005 | doi:10.1038/nbt1128
Abstract | Full text | PDF
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New plant gene could help allay concerns over GM crops

Nature Biotechnology pp 1177 - 1180

A newly identified plant gene that could change the way we develop GM plants is reported in the September issue of Nature Biotechnology. The naturally antibiotic resistant gene, found in thale cress (Arabidopsis thaliana), could provide a strong alternative to current practices, say Neal Stewart and colleague.

Traditionally, GM plants have been engineered with bacterial antibiotic resistance markers (ARMs) to help effectively identify which seedlings have taken up transgenes. The successful plants grow because of their resistance to antibiotics. This method of 'hooking up' antibiotic-resistance genes to transgenes of interest has been widely used in plant research since the 1980s. One major, theoretical health and safety concern over this practice has been the potential for 'reverse' horizontal gene transfer (HGT) back to bacteria — ingesting GM plants could increase our immunity to the antibiotics used in this engineering process.

The thale cress gene AtWBC19 has the potential to be used in place of bacterial ARMs, say the authors. Overexpression of this gene causes resistance to the common antibiotic kanamycin in tobacco plants. Belonging to a group of proteins that specialise in capturing and evicting toxins in plants, AtWBC19 works as effectively against kanamycin as conventional bacterial resistance genes — such as the nptII gene (neomycin phosphotransferase II) from Escherichia coli. Because of the difference in cell structure and the mechanisms that drive both bacterial and plant cells, the team says that it is highly unlikely that acquisition of the gene by a bacterium could confer antibiotic resistance.

As a plant gene destined for use in plants, AtWBC19 overcomes theoretical concerns over the combination of genetic material across kingdom boundaries. Also, AtWBC19 may prove a valuable substitute for nptII in the development of soybean, cotton, Brassica and Solanaceae crops (cabbage and potato family crops), as well as some forest tree species, argue the researchers.


Overexpression of an Arabidopsis thaliana ABC transporter confers kanamycin resistance to transgenic plants pp 1177 - 1180
Ayalew Mentewab & C Neal Stewart Jr
Published online: 21 August 2005 | doi:10.1038/nbt1134
Abstract | Full text | PDF
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ISSN: 1087-0156
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