SIMAAN A. Jalila

SIMAAN A. Jalila

Location
Service 342
Telephone
04 13 94 56 20
Status
DR or equivalent
Team
BiosCiences

Career path

2016: CNRS director (Marseille)

2002: CNRS researcher in Marseille

2000-2001 : Postdoc in Raman Spectroscopy with Prof. Peter Hildebrandt/ Max Planck Institut für Strahlenchemie, Mülheim / Ruhr (Allemagne) et à Instituto de Tecnológia Química e Biológica, Oeiras (Portugal)

1997-2000 : PhD in Bioinirganic chemistry, Paris-Sud University (Orsay) / Prof Jean-Jacques GIRERD and Frédéric Banse

1996 : «Agrégation externe de Sciences Physiques Option Chimie ».

1993 -1997: Student at the « Ecole Normale Supérieure de Cachan »  Chemistry department. Physical Chemistry studies at Université Paris-Sud, Orsay.

Honour

  • Ecole Normale Supérieure de Cachan scolarship (1993-1997)
  • PhD grant from French Ministry (1997-2000)
  • City of Marseille grant (2002)
  • Invited researcher at the university of Cuernavaca (UNAM), Mexico (2010)
  • City of Marseille attractivity trophee (2017)
  • Biomimetic Innovation Price -Region PACA (2019)

Research themes

Copper monooxygenases and bioinspired models

  • In collaboration with: Marius Réglier,  Bruno Faure, Alexandre Ciaccafava, Maylis Orio
  • current Ph.D students: Iris Wehrung (co-direction M. Orio; 2023-)
  • current postdocs : Khalil Youssef & Subhankar Sutradhar 

Formers students: Yongxing Wang (co-direction A. Martinez & M. Orio, 2021-2024); Rébecca Leblay (co-direction B. faure; 2021-2024); Manon Pujol (co-direction C. Decroos; 2019-2023); Stefani Gamboa (co-direction M. Orio; 2019-2023); Rogelio Gomez Pineiro (co-direction M. Orio; 2018-2021); Alessia Munzone (co-direction C. Decroos; 2017-2021), Marianthi Kafentzi (co-direction M. Réglier; 2013-2016)

Structure-fonction remationships of  Lytic Polysaccharide Monooxygenases

Conversion of biomass into biobased chemicals is an important strategy for the future. In particular, the use of non-edible parts of plants from agricultural or forestry residues (lignocellulosic biomass) for the production of “advanced” biofuels or chemicals, is highly desirable to avoid competition with food or water supplies. However, lignocellulose (mainly composed of cellulose, hemicellulose and lignin) valorization is still a challenge and its natural resistance to deconstruction is largely responsible for the high conversion costs. 

 Lytic Polysaccharide Monooxygenases or LPMOs are fungal of bacterial enzymes that boost recalcitrant polysaccharide deconstruction via oxidative mechanisms. LPMOs catalyze the hydroxylation of a strong C-H bond at the glycosidic linkage in the presence of dioxygen and electrons or hydrogen peroxide, further leading to chain breakage (Fig. 1A).  LPMO 's active site is composed of a mononuclear surface-exposed copper ion coordinated by two histidines including the N-terminal histidine bound in a bidentate fashion both by the imidazole side-chain and the amino terminus function(Fig. 1B). This unusual binding mode has been named Histidine-brace. 

Our studies are mainly centered on chitin-active bacterial LPMOs from AA10 family (https://www.cazy.org). Using a interdisciplinary approach ranging from chemistry to biology and biophysics (Fig. 3C), we aim at understanding the main mechanistic features, the influence of environmental parameters and of the nature of the cofactors, of the first and second coordination sphere as well as the interaction with the extended substrate. 

Figure 1. A) C1 oxidation of chitin catalysed by LPMO. B) Structure of a LPMO (PDB ID 6t5z) and zoom on the active site and the "histidine-brace" coordination motif. The axial amino acid may be tyrosine or phenylalanine. In the case of some fungal LPMOs, imidazole methylation of the N-terminal histidine is present (R = Me). C) Exemple of studies carried on in the group (Munzone et al. Inorg Chem 2024, 63(24), 11063).

External collaborations: Prof. Serena DeBeer (MPI, Mülheim-Ruhr, Allemagne); Dr. Guido Pintacuda (CRMN, CNRS, Lyon); Dr. Sylvain Bertaina (IM2NP, CNRS, Marseille); Dr. Christelle Hureau (LCC, CNRS, Toulouse).

 

Bioinspired model complexes

We synthesize bioinspired metal-containing complexes for small molecule activation (e.g. O2, H2O, H2) in order to understand the mechanisms at play, isolate and characterize reactive intermediate species, but also propose functional and catalytic systems operating under mild conditions.

Figure 2. Biomimetic approches. Example of LPMO bioinspired complex, detection of a reactive intermediate and activity assay on a model substrate.

In particular, we have prepared LPMO-bioinspired models for biomass degradation (Biomimetic innovation prize Région PACA 2019). We prepare copper complexes and metallopeptides mimicking the main structural and functional characteristics of LPMOs . We have settled several screening assays of LPMO-like activities on soluble model substrates and obtained proof-of-concept that some complexes can be used for extended polysaccharide deconstruction (Fig. 2; Leblay et al. ChemCatChem, 2023, 15(23), e202300933).

External collaborations : Dr. Catherine Belle, Dr. Hélène Jamet and Dr. Aurore Thibon-Pourret (Université Grenoble-Alpes / CNRS); Dr. Nicolas Le Poul (Université de Bretagne Occidentale, CNRS); Prof. Ivan Castillo (UNAM, Mexico, ECOS-Nord project); Dr. Laurent Heux (CERMAV, CNRS, Grenoble).

 

ACC Oxidase, a non-heme iron(II) enzyme

PhD student (past): Dr. Eugénie Fournier (with Prof. V. Belle, 2015-2018)

The plant hormone ethylene is essential for many aspects of plant life germination, senescence, fruit ripening and defense mechanisms. Ethylene is directly biosynthesized from 1-aminocyclopropane carboxylic acid (ACC), a metabolite of methionine. This step is catalyzed by ACC Oxidase a non-heme iron(II) containing enzyme. The conversion of ACC into ethylene requires the presence of ferrous ions, dioxygen and ascorbate. In addition, ACCO also requires the presence of CO2 (or HCO3-) for activity.

The crystallographic structures revealed a coeur folded in beta barrel that contains the active site. The iron(II)  ion is coordinated by the side chains of 2 histidines and one aspartate in a classical facial triad. Although several set of structures have been obtained, there are still question on the active conformation of the enzyme and in particular, that of the C-terminal part (in red on the figure ).Thanks to an interdisciplinary approach we aim at getting more information on this enzyme 

Our studies are centered on:

  • Understanding the mode of action of the enzyme
  • Exploring metal / activity modification
  • Getting information on the active conformation and dynamic of the C-terminal part
  • preparing model complexes
  • using ACCO as a platform to develop artificial enzymes

External collaborations: Prof. Valérie Belle and Dr. Marlène Martinho (Université d'Aix-Marseille); Prof. Christian Limberg (Humboldt University, Berlin, Germany); Dr. Wadih Ghattas (Université Paris-Saclay); Prof. Sam De Visser (Univ. Manchester, UK).

Fundings (last 10 years)

  • Project AMIDEX DYNACCO (coordinator); 2015-2018; 434 k€ (@iSm2 = 180 k€)
  • Project ANR PRCI (ANR-DFG) CUBISM (coordinator, ANR-18-CE92-0040); 2019-2023; (@iSm2 = 153 k€)
  • Project ANR COSACH (partner, ANR-22-CE07-0032); on-going; 458 k€ (@iSm2 = 149 k€)
  • project ANR INSPIRE (coordinator, ANR-23-CE43-0012); on-going; 496 k€ (@iSm2 = 175 k€)
  • project ANR LPMO-PEPS (partner, ANR-24-CE07-6490); on-going; 398 k€ (@iSm2 = 198 k€)
  • Project France 2030 PEPR BBEST PuLCO (coordinator, ANR-24-PEBB-0009); on-going; 1.4 M€ (@iSm2 = 280 k€)

Administrative responsabilities

Scientific outreach efforts

Diels-Alderases artificielles au service de la chimie verte. Wadih Ghattas, Jean-Pierre Mahy, Rémy Ricoux, A. Jalila Simaan, Marius Réglier

Techniques de l’Ingénieur, date publication le 10 septembre 2021, ref : IN404 V1

Author publications