Science - USA (2022-05-27)

SCIENCE science.org 27 MAY 2022 • VOL 376 ISSUE 6596 907

Engineered tomatoes get

a healthy dose of vitamin D

Knocking out a gene boosts precursors of essential nutrient

FOOD SCIENCE

T

omatoes get riper and tastier in the

summer Sun. Two studies now sug-

gest that with a little help from gene

editing, Sun-ripened tomatoes can also

stockpile a precursor molecule to vita-

min D, a vital nutrient normally found

mainly in animal products.

“This could be a game changer” in nations

where vitamin D deficiency is a problem, says

Esther van der Knaap, a plant geneticist at

the University of Georgia, Athens. Biofortified

plants could also help vegans get enough of

the nutrient. The finding “opens up a very ex-

citing new era for vitamin D,” says nutritional

scientist Susan Lanham-New of the Univer-

sity of Surrey.

Vitamin D helps regulate how the body

uses calcium, leading to stronger bones. And

there’s some evidence that low levels can

raise the risk of heart disease

and other health problems.

Sunlight helps your body

synthesize the vitamin, as

ultraviolet B (UVB) radiation

converts a precursor in skin

into a form that the liver and

kidney transform into usable

vitamin D. But people living at high latitudes

often aren’t exposed to enough UVB, particu-

larly in winter, to avoid deficiency. And age or

darker skin can also slow synthesis.

Eating animal products—fish, eggs, and

liver—that contain precursors can help make

up the deficit. In addition, milk sold in the

United States and some other countries is

supplemented. For vegans, mushrooms and

yeast are a less effective source. Another op-

tion is to take supplement pills, which are

often made from lanolin, a waxy substance

secreted by sheep. (Sheep can get vitamin D

by licking the lanolin off their wool.)

Because tomatoes naturally make a key vi-

tamin D precursor, two groups thought some

genetic tweaking could turn them into an

animal-free source of the vitamin.

This week in Nature Plants, a team led by

Cathie Martin, a plant metabolic engineer

at the John Innes Centre, reported that dis-

abling a single gene created tomatoes that

could each provide 20% of the recommended

daily allowance of vitamin D in the United

Kingdom. And in a March preprint posted

at Research Square, a group led by plant ge-

neticist Sunghwa Choe of Seoul National Uni-

versity reported that disabling a related gene

produced tomatoes with even higher levels of

vitamin D precursors.

Normally, tomatoes make a precursor

called provitamin D3 but convert it into other

compounds using enzymes coded for by two

genes, 7-DR1 and 7-DR2. These compounds

help the plant grow and protect it from stress.

The researchers suspected that knocking out

either of these genes would cause the plant

to accumulate provitamin D3, which when

exposed to sunlight transforms into a second

precursor—previtamin D3—that people can

use. Leaving the other gene intact would help

the plant function normally. “This seemed

like a real opportunity,” Martin says.

It worked. Martin’s team knocked out

7-DR2, producing tomatoes that, after ripen-

ing and exposure to sunlight, offered as much

previtamin D3 as two medium

eggs. The content can be in-

creased by slicing the tomato

first, and likely even more by

drying them in the Sun.

Choe’s group disabled the

other gene, 7-DR1. Although

the researchers did not expose

the biofortified fruit to UVB, they estimate

that each tomato can contain up to 100 mi-

crograms of provitamin D3. Levels remained

high after a month of freeze-dried storage.

“We think that the molecule is pretty stable

in the fruit,” Choe says.

So far, the modified tomatoes have been

grown only in laboratory greenhouses. Field

tests will be crucial to seeing whether the

plants can thrive under real-world stress, and

Martin will begin a field trial next month.

Choe hopes to start one this summer. Re-

searchers will also need to show that the

body can absorb the previtamin D3 in the

tomatoes and convert it to vitamin D.

Despite the potential benefits, some con-

sumers might not accept gene-edited toma-

toes, notes Kevin Cashman, a nutritional

scientist at University College Cork. But if

biofortified tomatoes do make it to mar-

ket, plant physiologist Dominique Van Der

Straeten of Ghent University writes in a com-

mentary in Nature Plants, they could mark “a

leap forward in decreasing our dependence

on animal-based foods.” j

By Erik Stokstad

“A very exciting new

era for vitamin D.”

Susan Lanham-New,

University of Surrey

is actively causing liver failure, you can’t go
near that patient with immune-suppressive
drugs,” which can hobble the body’s ability
to fight active infection.
Petter Brodin, a pediatric immunologist
and pediatrician at Imperial College Lon-
don and Moshe Arditi, a pediatric infectious
disease physician at Cedars-Sinai Medi-
cal Center, earlier this month published a
hypothesis knitting the two viruses together.
They noted that many of the cases tested in
the United Kingdom harbored adenovirus-
41, a strain that infects the gut, and that
SARS-CoV-2 has been found to establish gut
reservoirs that persist after acute infection.
Brodin and Arditi proposed that after
adenovirus infects the gut, coronavirus
might act as a coconspirator. A small section
of the SARS-CoV-2 spike protein that has
been shown to prompt a broad activation
of T cells might supercharge the immune
response to adenovirus, and the rogue im-
mune response might then attack the liver.
Such a mechanism, in which a piece of the
coronavirus spike protein triggers an im-
mune overreaction, has been implicated in
the serious inflammation found in MIS-C.
Brodin urges clinicians to test stool and
other samples for intestinal SARS-CoV-2
and a hyperactivated immune system. If
the hypothesis is confirmed, he says im-
munosuppressive therapy would be appro-
priate. “[If ] it’s an out-of-control activation
of the immune system, then you need to be
very aggressive in shutting down that im-
mune response.”
Jalali, for his part, is worried by a pre-
print, not yet peer reviewed, posted on
14 May by scientists at Case Western Reserve
University. The paper suggests the hepati-
tis cases are the tip of an iceberg of liver
damage in children post–COVID-19. The re-
searchers compared the electronic records
of 246,000 children who got COVID-19 be-
tween March 2020 and March 2022 with
those of 551,00 children who contracted
other respiratory infections in that period.
In the months after infection, COVID-19 in-
fected children were 2.5 times more likely
to have elevated levels of enzymes that indi-
cate liver damage, and 3.3 times more likely
to have elevated bilirubin, which can also
indicate impaired liver function.
Clare Wenham, a global health policy
expert at the London School of Economics
whose 4-year-old son was hospitalized with
hepatitis this month and treated with sup-
portive care, has been tracking the battling
theories of causation. “There just aren’t
enough data to really make any firm conclu-
sions yet,” she says. “You’re with your clini-
cians and they’re like: ‘We just don’t really
know ... what the trajectory is going to be.’
That’s what’s scary as a parent.” j