Biocatalysis Position In Green Chemistry

How Green is Biocatalysis? To Calculate is To know Yan Ni, Dirk Holtmann and Frank Hollmann ChemcatChem 2014, 6, 930-945

http://www.nature.com/scitable/topicpage/cell-metabolism-14026182

DEFINITIONS AND CONCEPTS

+

A chemical reaction model:

Molecule 1 Molecule 2

= Molecule 3 Molecule 4

Organic synthesis concept

+ = Molecule 3

Molecule 6

Molecule 5

Organic synthesis is concerned with the construction of molecules, involving chemical reactions. Several reactions will take place one after another (or in parallel) until the targeted molecule is complete.

Molecule 3

Boot’s process for ibuprofen (analgesic like aspirin) synthesis

(1960) : 6 steps and numerous non

recyclable waste.

Example

Green Chemistry

1990 U.S. Environmental Protection Agency (EPA)

1998 12 principles of green chemistry by P. Anasta and J. Warner

Reduce the impact of chemistry on the environment by preventing pollution at its source and using fewer natural resources

Green chemistry efficiently utilizes (preferably renewable) raw materials, eliminates waste and avoids the use of toxic and/or hazardous reagents and solvents in the manufacture and application of chemical products.

2007 REACH European rules : to secure production and utilisation of chemicals

12 principles of Green Chemistry

Green Chemistry

Atom economy

Efficient production

Innocuous degradation

products

Preventing waste

Diminishing accidents

Save energy

Renewable feedstock

Real time measurement

Avoid derivatisations

Avoid auxiliary substances

Non-toxic substances

Catalysts

New process by BHC (1990): only 3 steps and only one sub-product (acetic acid) which is recycled for another use.

Example « Green process »

WILLSTÄTTER RICHARD - (1872-1942) Nobel price in 1915 chlorophyll and other plant pigments

"The vast number of chemical reactions taking part in a living cell are controlled by organic catalysts. Life is the orchestrated combination of processes catalyzed by enzymes."

Biocatalysis may be broadly defined as the use of enzymes or whole cells as biocatalysts for industrial or academic synthetic chemistry.

Biocatalysis

Enzyme ubiquity and diversity

Escherichia coli Human

~ 25000 genes ~ 20000 proteins ~ 15000 enzymes

4500 genes 1518 enzymes 1700 reactions

Nature, a molecule architect?

Eukaryotic cell Prokaryotic cell

Nature, a molecule architect?

Orchestration? Metabolic map…

Huge diversity of natural Compounds … and reactions

CHEMOSELECTIVITY, REGIOSELECTIVITY, STEREOSELECTIVITY

To give an idea: our Universe would contain 1080 atoms in the “eye accessible” part

An average protein would contain 300 aa and as 20 proteinogenic amino acids exist, 20300 (10390) different polymers are theoretically possible… The complete Universe is insufficient to contain a copy of each protein. An enzyme is thus able to bind a substrate specifically to lead to a chemical reaction.

Enzymes are chemoselective, regioselective and stereoselective

Chemoselectivity: reaction on a polyfunctional molecule possible without any protection. Regioselectivity: Identical functional groups distinguished depending on their position on the molecule. Stereoselectivity: enzymes are chiral catalysts. They are able to differentiate stereoisomers and in particular enantiomers.

How this can work?

From gene to protein

From gene to protein

Enzymes are proteins

Proteins are polymers (macromolecules) built up from amino acids.

Amino acids Dipeptide Oligopeptide

…

Protein

Organisation and folding of this chain lead to a 3D structure.

Enzymes are proteins

Cartoon representation

cristal

Soybean protein

They « cut » molecular assemblies into smaller molecules

They « stick » for constructing molecular assemblies

+ =

= +

Enzymes at work

Key and lock concept

Enzymes at work

http://biosciences.dupont.com/about-us/guide-to-industrial-enzymes/

http://culturesciences.chimie.ens.fr/dossiers-reactivite-catalyse-autresdocs-Enzymes_Laage_1.html#menu

http://www.classhelp.info/Biology/AUnit3Biochemistry.htm

Enzymes at work

http://science.halleyhosting.com/sci/ibbio/chem/notes/chpt8/chpt8.htm

http://www.nature.com/scitable/topicpage/protein-function-14123348

Rate factor increase from 107 to 1017 depending on the enzyme

Enzymes at work

http://www.geni.org/globalenergy/library/technical-articles/generation/future-fuels/iogen/enzyme-technology/index.shtml

How industrial enzymes are made? And in the lab?

Enzymes production

How enzymes are used?

However… Enzymes are denatured by a change in temperature, pH or chemical action

http://www.rsc.org/learn-chemistry/resources/chemistry-in-your-cupboard/vanish/8

In water, buffer, low temperature, mild conditions…

inactive

APPLICATIONS

Detergent, food, pharmaceutical, chemical and leather industries… are producing and/or using enzymes

https://chempics.wordpress.com/category/industrial-chemistry/

In food? Vanillin Industrial synthesis, artificial aroma

(From lignin)

.

Enzymes at home?

http://www.teknoscienze.com/Articles/HPC-Today-Detergent-enzymes-ndash-from-discovery-to-product-The-power-of.aspx#.U3eWhXJPHqM

Amylase

Cellulase

Protease

Microorganisms Tailored to the Raw Materials Available Ethanol is produced from non-food biomass such as farming and forest waste, green waste and dedicated crops. This involves extracting the cell wall (cellulosic) sugar from biomass utilizing enzymes that convert cellulose into sugar (glucose) through hydrolysis. Then yeast strains convert the sugars into ethanol via fermentation. The resultant ethanol is distilled to ensure it is of suitable quality for use as biofuel. For this biotechnology process to be profitable, more efficient enzymes are needed, which is a core focus of R&D in this area

http://total.com/en/energies-expertise/renewable-energies/biomass/projects-achievements/futurol

In cars? Bioethanol

CELL FACTORIES

http://www.nature.com/nchembio/journal/v8/n6/fig_tab/nchembio.970_F1.html

Categories of chemicals produced by cell factories

How to get efficient desired enzymes?

Efficient biocatalysts for fine green chemistry or

industrial chemistry

Biodiversity

De novo design (computer modelling) Directed evolution of

existing enzymes

Directed evolution

??

Desired biocatalyst

Wild-type biocatalyst

Directed evolution

NEW GENES => NEW ENZYMES WITH NEW PROPERTIES => SCREENING

Evolution Molecular biology

Screening

From biodivsersity

Harvest the DNA (genes) from the environment

Databases

Screening for the desired properties

New enzymes

http://www.uniprot.org http://www.rcsb.org/pdb/home/home.do http://biology.unm.edu/biology/maggieww/Public_Html/ANALYSIS.HTM (list of databases)

CONCLUSION

12 principles of Green Chemistry

Green Chemistry

Atom economy

Efficient production

Innocuous degradation

products

Preventing waste

Diminishing accidents

Save energy

Renewable feedstock

Real time measurement

Avoid derivatisations

Avoid auxiliary substances

Non-toxic substances

Catalysts

BIOCATALYSIS HAS A PRIVILEGED POSITION IN GREEN CHEMISTRY!