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Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs).

ABSTRACT: Carotenoid cleavage dioxygenases (CCDs) comprise a superfamily of mononuclear non-heme iron proteins that catalyze the oxygenolytic fission of alkene bonds in carotenoids to generate apocarotenoid products. Some of these enzymes exhibit additional activities such as carbon skeleton rearrangement and trans-cis isomerization. The group also includes a subfamily of enzymes that split the interphenyl alkene bond in molecules such as resveratrol and lignostilbene. CCDs are involved in numerous biological processes ranging from production of light-sensing chromophores to degradation of lignin derivatives in pulping waste sludge. These enzymes exhibit unique features that distinguish them from other families of non-heme iron enzymes. The distinctive properties and biological importance of CCDs have stimulated interest in their modes of catalysis. Recent structural, spectroscopic, and computational studies have helped clarify mechanistic aspects of CCD catalysis. Here, we review these findings emphasizing common and unique properties of CCDs that enable their variable substrate specificity and regioselectivity. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

SUBMITTER: Daruwalla A

PROVIDER: S-EPMC7308199 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genomewide analysis of carotenoid cleavage dioxygenases in unicellular and filamentous cyanobacteria.

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Comprehensive Analysis of Carotenoid Cleavage Dioxygenases Gene Family and Its Expression in Response to Abiotic Stress in Poplar.

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Identifying <i>Bixa orellana</i> L. New Carotenoid Cleavage Dioxygenases 1 and 4 Potentially Involved in Bixin Biosynthesis.

Project description:Carotene cleavage dioxygenases (CCDs) are a large family of Fe2+ dependent enzymes responsible for the production of a wide variety of apocarotenoids, such as bixin. Among the natural apocarotenoids, bixin is second in economic importance. It has a red-orange color and is produced mainly in the seeds of B. orellana. The biosynthesis of bixin aldehyde from the oxidative cleavage of lycopene at 5,6/5',6' bonds by a CCD is considered the first step of bixin biosynthesis. Eight BoCCD (BoCCD1-1, BoCCD1-3, BoCCD1-4, CCD4-1, BoCCD4-2, BoCCD4-3 and BoCCD4-4) genes potentially involved in the first step of B. orellana bixin biosynthesis have been identified. However, the cleavage activity upon lycopene to produce bixin aldehyde has only been demonstrated for BoCCD1-1 and BoCCD4-3. Using in vivo (Escherichia coli) and in vitro approaches, we determined that the other identified BoCCDs enzymes (BoCCD1-3, BoCCD1-4, BoCCD4-1, BoCCD4-2, and BoCCD4-4) also participate in the biosynthesis of bixin aldehyde from lycopene. The LC-ESI-QTOF-MS/MS analysis showed a peak corresponding to bixin aldehyde (m/z 349.1) in pACCRT-EIB E. coli cells that express the BoCCD1 and BoCCD4 proteins, which was confirmed by in vitro enzymatic assay. Interestingly, in the in vivo assay of BoCCD1-4, BoCCD4-1, BoCCD4-2, and BoCCD4-4, bixin aldehyde was oxidized to norbixin (m/z 380.2), the second product of the bixin biosynthesis pathway. In silico analysis also showed that BoCCD1 and BoCCD4 proteins encode functional dioxygenases that can use lycopene as substrate. The production of bixin aldehyde and norbixin was corroborated based on their ion fragmentation pattern, as well as by Fourier transform infrared (FTIR) spectroscopy. This work made it possible to clarify at the same time the first and second steps of the bixin biosynthesis pathway that had not been evaluated for a long time.

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