SYNTHETIC BIOLOGY
Designed enzyme rescues live bacteria Protein designed from scratch is efficient enough to perform essential biological function in cells
low-iron conditions. The natural esterase’s activity also lets bacteria thrive in low-iron media. But Syn-IF showed no detectable enzymatic activity. So the researchers mutated it and screened for mutants that other de novo enzymes that work in cells. It’s hard to get proteins designed from sustained low-iron bacteria better than F. Akif Tezcan’s group at the University scratch, called de novo proteins, to catSyn-IF did. The result was Syn-F4, which of California, San Diego, previously mutatalyze reactions nearly as efficiently as ed a natural redox protein to perform β-lac- catalyzed the same reaction as the natural native enzymes do. Although de novo-deesterase. tamase activity in bacteria. And Hecht’s signed proteins have shown off their The new study “is significant and exgroup showed earlier that a de novo protein catalytic prowess in lab glassware, getting citing,” says Ivan V. Korendovych of Syrcould sustain living bacteria lacking an esthem to catalyze reactions at levels that acuse University, O because Syn-F4 O O O O O O O OO works catalytically Ferric O NH OH O OH in bacteria and has HO HO enterobactin O OH O O HO esterase O NH O NH O NH O NH a simple four-helix or Syn-F4 O NH O NH O NH O O HN + + structure, raising O OH OH OH OH OH OH 2+ O the possibility of Fe O 3+ O Fe designing comparaOH OH OH OH OH OH O bly simple proteins O Trimer Dimer Monomer that catalyze other Ferric reactions in live Syn-F4 catalyzes the conversion of ferric enterobactin to monomer, dimer, and trimer enterobactin organisms. products, just as the native enzyme ferric enterobactin esterase does. Syn-F4 “not sential gene, but the protein most likely did only replaced the function of a naturally can affect the biology of living organisms evolved enzyme but, remarkably, used a so by nonenzymatic means. The new study hasn’t been easy. completely different sequence, structure, shows that a de novo protein can play an Michael H. Hecht and coworkers at and mechanism to do so,” adds Burckhard essential catalytic role in cells. Princeton University have now done so Seelig of the University of Minnesota. Hecht’s group started with a de novo by designing a de novo protein that sus“The ability to create nonnatural enfour-helix protein called Syn-IF. When tains living bacteria genetically modified zymes that function in a living organism expressed in Escherichia coli mutated to to require the protein’s catalytic activity is crucial to realize the hopes of synthetic remove ferric enterobactin esterase, Syn(Nat. Chem. Biol. 2018, DOI: 10.1038/ biology.”—STU BORMAN IF allowed the microbes to survive under nchembio.2550). The work could lead to
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A comic collaboration between C&EN and ChemScrapes cartoonist Brendan Burkett
More online To see more of Burkett’s chemistry cartoons, go to chemscrapes.net. To see more Sketch Chemistry, visit cenm.ag/sketch.
JANUARY 22, 2018 | CEN.ACS.ORG | C&EN
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