Ancient Rubiscos, Resurrected

Proteins from Nightshade plants were expressed in E. coli, and could fix carbon dioxide faster than modern Rubisco.

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Hello. Ancient RuBisCOs are brought back to life in engineered bacteria. Chemical reprogramming shifts cells back to a pluripotent state. And a look at gut dysbiosis, and how to prevent it.

Ancient Rubiscos

Rubisco sucks. This protein behemoth takes carbon dioxide from the air and fixes it into sugar between 2 and 5 times per second. That’s excruciatingly slow. Rubisco often mistakes carbon dioxide for regular oxygen because it evolved 2.4 billion years ago, before the earth became laden with oxygen and mammals grew to fifty feet tall. It evolved on a carbon-rich planet.

For a new study, researchers predicted the sequence of ancient Rubiscos from nightshade plants and then created them in the lab. Nightshades have a C3 form of Rubisco, and these proteins can be inserted into E. coli bacteria and Nicotiana tabacum, or tobacco plants (both common, model organisms), with ease. The most important food crops are C3 plants: cowpea, soybean, rice. But Rubiscos are much faster in C4 plants. If food plants had a better Rubisco, they could grow larger with less energy to feed a swelling population.

The ancient Rubiscos, expressed in E. coli, had enzyme activities “similar to those from C4 Rubiscos and exhibit significantly higher catalytic efficiency than both C3 and C4 Rubiscos,” the authors write. “We hypothesize that some of these ancestors could predate the emergence of C4 photosynthesis in several other families and illustrate the evolutionary mechanism of C3 Rubisco through past climate changes.”

By looking to the past, plants can be engineered for the future.

Read more at Science Advances.

On Metchnikoff

Ilya Metchnikoff discovered phagocytosis, and phagocytes, in 1882. He coined the term gerontology in 1903. He pushed people to eat yogurt, rich in Lactobacillus, to prolong lifespans and keep a healthy gut (and was widely panned by the media for it). He shared the Nobel Prize in Physiology or Medicine, together with Paul Ehrlich, in 1908. The father of immunology, the standard-bearer for the notion that the gut is teeming with life, Metchnikoff pioneered the idea that the gut’s health underlies the body’s health.

Taking antibiotics to treat an illness, though, shifts the gut’s natural composition in unhealthy ways. Antibiotic resistance can arise. That’s bad. In a new study, Lactococcus lactis bacteria were engineered to degrade β-lactam antibiotics, without developing antibiotic resistance.

The microbes were engineered to produce two proteins that are each released into the extracellular environment. Once there, they fuse together to form a single, active protein that breaks down antibiotics. This strategy worked: Engineered L. lactis microbes were not resistant to ampicillin, and their ability to break down and resist antibiotics emerged only after the cells grew to a critical population threshold.

When placed inside mice, the antibiotic-fighting microbes also “minimized gut dysbiosis without affecting the ampicillin concentration in serum.” These modified microbes, then, could prevent some of the negative effects caused by antibiotic treatments. Metchnikoff would be proud.

Read more at Nature Biomedical Engineering.

Holy Grail

Reverting a somatic cell back to its pluripotent state is usually done by bombarding it with transcription factor proteins that go into each cell’s nucleus and switch on specific genes. Doing the same, but with chemicals, is far more difficult.

A new study explains how human somatic cells can be reverted to pluripotent stem cells using purely chemical reprogramming, using a process similar to that used by axolotls to regenerate limbs. The experimental technique takes between 39 and 52 days.

This study offers a new way to generate patient-specific pluripotent stem cells for clinical-grade cell manufacturing, according to many of the 1,000+ people who have already tweeted about it.

Read more at Nature.