TY - JOUR
T1 - Control of carotenoid biosynthesis through a heme-based cis-trans isomerase
AU - Beltrán, Jesús
AU - Kloss, Brian
AU - Hosler, Jonathan P.
AU - Geng, Jiafeng
AU - Liu, Aimin
AU - Modi, Anuja
AU - Dawson, John H.
AU - Sono, Masanori
AU - Shumskaya, Maria
AU - Ampomah-Dwamena, Charles
AU - Love, James D.
AU - Wurtzel, Eleanore T.
N1 - Funding Information:
We thank W. Hendrickson (Columbia University and New York Consortium on Membrane Protein Structure) for helpful discussions and use of the New York Structural Biology Center facilities. We thank M. Inouye (University of Medicine and Dentistry of New Jersey) for valuable advice on codon optimization and L. Bradbury (Lehman College and CUNY) for helpful discussions. E.T.W. was funded by the US National Institutes of Health (grant GM081160), CUNY and Lehman College. E.T.W. was also supported by travel funds from the Gordon Research Conferences to attend the Metals in Biology Gordon Research Conference, where E.T.W. was able to initiate collaborations with heme experts J.P. Hosler, A. Liu and J.H. Dawson through much-appreciated help from H. Gray (California Institute of Technology). The New York Consortium on Membrane protein structure (B.K. and J.D.L.) was supported through funds obtained from the US National Institutes of General Medical Sciences Protein Structure Initiative (PSI) program (grant GM095315). J.H.D. was funded by the US National Institutes of Health grant GM 26730; A.L. was funded by US National Institutes of Health grant R01GM108988 and the Georgia Research Alliance Distinguished Scholar Program. C.A.-D. was funded by The New Zealand Institute for Plant and Food Research Limited, New Zealand.
Publisher Copyright:
© Nature America, Inc. All rights reserved.
PY - 2015/8/23
Y1 - 2015/8/23
N2 - Plants synthesize carotenoids, which are essential for plant development and survival. These metabolites also serve as essential nutrients for human health. The biosynthetic pathway for all plant carotenoids occurs in chloroplasts and other plastids and requires 15-cis-ζ-carotene isomerase (Z-ISO). It was not known whether Z-ISO catalyzes isomerization alone or in combination with other enzymes. Here we show that Z-ISO is a bona fide enzyme and integral membrane protein. Z-ISO independently catalyzes the cis-trans isomerization of the 15-15′ carbon-carbon double bond in 9,15,9′-cis-ζ-carotene to produce the substrate required by the subsequent biosynthetic-pathway enzyme. We discovered that isomerization depends upon a ferrous heme b cofactor that undergoes redox-regulated ligand switching between the heme iron and alternate Z-ISO amino acid residues. Heme b-dependent isomerization of a large hydrophobic compound in a membrane was previously undescribed. As an isomerase, Z-ISO represents a new prototype for heme b proteins and potentially uses a new chemical mechanism.
AB - Plants synthesize carotenoids, which are essential for plant development and survival. These metabolites also serve as essential nutrients for human health. The biosynthetic pathway for all plant carotenoids occurs in chloroplasts and other plastids and requires 15-cis-ζ-carotene isomerase (Z-ISO). It was not known whether Z-ISO catalyzes isomerization alone or in combination with other enzymes. Here we show that Z-ISO is a bona fide enzyme and integral membrane protein. Z-ISO independently catalyzes the cis-trans isomerization of the 15-15′ carbon-carbon double bond in 9,15,9′-cis-ζ-carotene to produce the substrate required by the subsequent biosynthetic-pathway enzyme. We discovered that isomerization depends upon a ferrous heme b cofactor that undergoes redox-regulated ligand switching between the heme iron and alternate Z-ISO amino acid residues. Heme b-dependent isomerization of a large hydrophobic compound in a membrane was previously undescribed. As an isomerase, Z-ISO represents a new prototype for heme b proteins and potentially uses a new chemical mechanism.
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U2 - 10.1038/nchembio.1840
DO - 10.1038/nchembio.1840
M3 - Article
C2 - 26075523
AN - SCOPUS:84937514111
SN - 1552-4450
VL - 11
SP - 598
EP - 605
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 8
ER -
