Atlanta: A research team’s discovery of new information about how plants synthesize carotenoids, precursors for vitamin A that are essential for plant development and survival, and human health, could help scientists increase the levels of provitamin A in food crops and reduce global vitamin A deficiency. The World Health Organization estimates 250 million children suffer from vitamin A deficiency.
Vitamin A deficiency is the leading cause of preventable blindness and
increases the risk of disease and death from severe infections. It is a
public health problem in more than half of all countries, especially in
Africa and Southeast Asia, having a significant impact on young children
and pregnant women in low-income countries, according to the World
This global problem has sparked worldwide efforts to increase the
levels of provitamin A carotenoids in food crops. To achieve this,
scientists must gain further knowledge of how plants control and
biosynthesize carotenoids that can be converted to vitamin A in humans.
The findings, published June 15 in Nature Chemical Biology, highlight
the team’s discovery of a new enzyme that is critical for the
biosynthesis of vitamin A in plants and its unexpected dependence on
heme iron. This heme iron allows the enzyme to make the necessary
structural changes to complete the chemical mechanism for making vitamin
Scientists from Georgia State University, City University of New
York, New York Structural Biology Center, University of Mississippi
Medical Center, University of South Carolina, Georgia Institute of
Technology, New Zealand Institute for Plant and Food Research Limited
and Albert Einstein College of Medicine collaborated to find out how
vitamin A is synthesized in plants.
This study confirmed that 15-cis-ζ-carotene isomerase (Z-ISO) is an
enzyme and integral membrane protein. It also found that Z-ISO
independently catalyzes the cis-trans isomerization, or chemical
reaction that changes the structural conformation of a compound, of the
central carbon double bond to produce the required molecule upon which
the enzyme acts for the pathway.
“We identified this enzyme plays a significant role in synthesizing
vitamin A. This is one critical step to get vitamin A compounds,” said Dr. Aimin Liu,
Distinguished University Professor of chemistry and biochemistry at
Georgia State. “It is really unique in the biosynthetic pathway because
it’s a relatively large-sized organic molecule. Until recently, it
wasn’t known which gene product is responsible for these reactions.”
Liu and his group used electron paramagnetic resonance (EPR)
spectroscopy, which is extremely sensitive to electronic structures, and
concluded that Z-ISO is a heme-based protein. Heme is a large, organic
system with a metal iron in the center. It is well known because of its
red color and presence in red blood cells.
“It’s quite surprising to us for a chemical reaction to use heme,”
Liu said. “It’s really new for the chemical field. It’s a really large
molecule, a very long chain with many double and single bonds. It does
not typically allow large molecules to come in. There’s not much room to
play. We discovered surprisingly that it’s an isomerase reaction
catalyzed by a heme protein.”
EPR spectroscopy revealed the heme center starts as Fe(III) and is
reduced to Fe(II), creating room for structural change and a pocket for
the Z-ISO enzyme. The heme center rotates the Z-ISO enzyme 180 degrees
from the cis orientation, with two groups on the same side, into the
thermodynamically favorable trans orientation, which has two groups on
opposite sides. The reduction from Fe(III) to Fe(II) is necessary for
enzyme activity, Liu said.
“After that, the product can become vitamin A. You still need one to
two steps to complete synthesis of vitamin A, but this is the most
intriguing step chemically,” Liu said.
The findings are significant for those interested in vitamin
synthesis, plant biology, plant biochemistry, enzymology and heme
proteins, he said.
“It’s important to understand this molecular mechanism so in the
future we could generate synthetic compounds or modify the forms for
different medical purposes,” Liu said.
The study is funded by the National Institutes of Health.