news and views
as a minimal genome with a minimal set of yeast can handle. Work in our group9 has adopted across the research community—only genes7. Growth of M. genitalium (which has begun to explore this in Bacillus subtilis. We a handful of laboratories around the world cur- an 0.58-Mb genome) is much slower than have created a hybrid ‘Cyanobacillus’ that sta- rently have the expertise and resources to carry M. mycoides (with a 1.08-Mb genome) or other bly possesses a 7.7-Mb genome through the out the kinds of experiments described by the mycoplasmas with larger genomes. The pres- addition of the Synechocystis genome (3.5 Mb) JCVI group. The question is—with only a few ent protocol described by Gibson et al.1 thus to B. subtilis (4.2 Mb)9. Addition of another groups around the world capable of working provides a useful system to understand how genome (5.0 Mb) to our Cyanobacillus strain on this technology—how large a gap needs to smaller sets of genes in different sets of combi- could potentially produce bacterial cells with be bridged between the mycoplasma genome nations are essential for growth. If genes from genomes of 12.7 Mb—larger than the genome described by Gibson et al.1 and the many other other bacteria can be codon optimized to work of yeast (12.5 Mb), which has one of the small- genomes of biological interest? in M. capricolum, ultimately the approach may est genomes of the eukaryotes for which full also prove useful in assessing the functions of genome sequences are available. COMPETING FINANCIAL INTERESTS The author declares no competing financial interests. nonculturable microorganisms that are abun- Ultimately, the importance of this break- dant in nature8, for which we have growing through in synthetic biology will depend 1. Gibson, D. et al. Science published online, doi:10.1126/ sequence information. Indeed, one day it may on further reductions in the cost of oligo- science.1190719 (20 May 2010). 2. Gibson, D. et al. Science 319, 1215–1220 (2008). be possible to use the system to study whole or nucleotide synthesis, extensions in the size 3. Lartigue, C. et al. Science 317, 632–638 (2007). partial plant or mammalian chromosomes. of artificial DNA molecules that can be con- 4. Gibson, D. et al. Nat. Methods 6, 343–345 (2009). Conversely, rather than investigating structed and demonstration that the principles 5. Carr, P.A. & Church, G.M. Nat. Biotechnol. 27, 1151– 1162 (2009). 1 minimal synthetic genomes, it should also described by Gibson et al. for mycoplasmas 6. Carlson, R. Nat. Biotechnol. 27, 1091–1094 (2009). be possible to amend new genes to existing can be applied more widely to other bacterial 7. Glass, J. et al. Proc. Natl. Acad. Sci. USA 103, 425– ‘natural’ genomes to design enlarged bacterial systems (e.g., Escherichia coli) more familiar to 430 (2006). 8. Colwell, R.R. & Grimes, D.J. (eds.) Nonculturable genomes. This raises a fundamental question the biology and biotech research communities. Microorganisms in the Environment (ASM Press, of what is the largest size possible for a cir- Unlike the recent advance in which induced Washington, DC, 2000). cular bacterial genome. In the Gibson et al.1 pluripotent stem cells were created from a 9. itaya, M., Tsuge, K., Koizumi, M. & Fujita, K. Proc. 102, 15971–15976 (2005). 10 Natl. Acad. Sci. USA protocol, the size of the synthesized genome small set of transcription factors —a break- 10. Takahashi, K. & Yamanaka, S. Cell 126, 663–676 is dependent on the largest molecule that through which was almost immediately widely (2006).
Antibiotic leads challenge conventional wisdom
Two recent papers in Science1,2 bacterial cell wall. At least of improved variants provide surprising twists to the four other defensins from and suggests that conventional views on how fungi and invertebrates more rigorous members of two extensively also inhibit the processing scrutiny of the studied classes of molecules of Lipid II. Plectasin or mechanisms of exert their effects. Whereas improved plectasin derivates other defensins is © 2010 Nature America, Inc. All rights reserved. All rights Inc. America, Nature © 2010 Schneider et al.1 reveal a have previously been shown warranted. new mechanism of action for to be effective against Nonribosomal a subset of defensins, Wyatt multidrug-resistant strains peptides are a et al.2 show that certain of Gram-positive bacteria, major class of nonribosomal peptides, a including methicillin-resistant bacterial secondary group of secondary metabolites Staphylococcus aureus. metabolites most commonly regarded as Remarkably, the antibiotic including—most without the nonribosomal antibiotics, might in fact be vancomycin—one of the famously—penicillin. Wyatt peptide synthetase gene cause promising drug targets. few remaining drugs in our et al.2 study the function much milder infections in mice Defensins are a family arsenal to treat multidrug- of a nonribosomal peptide and are unable to colonize of short antibiotic peptides resistant Gram-positive synthetase gene cluster that spleen, liver and heart. It conserved across the infections—also binds and is conserved universally remains to be seen whether fungal, animal and plant inhibits the processing of Lipid across Staphylococcus aureus investigation of the functions kingdoms3. Whereas most II. But fortunately, the authors strains, with orthologs in other of other nonribosomal peptides defensins are thought to observe no cross-resistance pathogenic staphylococci. might find similarly promising nonspecifically disintegrate between vancomycin and Although the products of drug targets. bacterial membranes due to plectasin and speculate that the synthetase, two cyclic Markus Elsner their amphipathic structures, the distinct binding sites of dipeptides named aureusimine 1. Schneider, T. et al. Science 328, 1 Schneider et al. show that the two molecules make the A and B, are not required 1168–1172 (2010). the fungal defensin plectasin emergence of cross-resistance for growth, the expression of 2. wyatt, X. et al. Science published instead targets cell wall unlikely. Identification of a virulence factors is greatly online, doi: 10.1126/science. 1188888 (3 June2010). biosynthesis by sequestering molecular target of plectasin reduced in their absence. 3. Ganz, T. Nat. Rev. Immunol. 3, 710– the Lipid II precursor of the may allow the rational design Staphylococcus aureus strains 720 (2003).
nature biotechnology volume 28 number 7 JULY 2010 689