Enzyme Engineering & Technology - acib

11Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions

Biocatalytic Synthesis

enzymatic solutions for chemical problems

Enzyme Engineering & Technology

enzymes designed for industry

science is our success


3designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions

Contents

educti e Biotransformations -

idati e Biotransformations -

- Bond ormation -

- Bond Brea ing

Enzymatic somerisation

ydrolysis Esteri cation -

Enzymatic ascades -

lycozyme Technology -

odi cation

n-silico Search for o el Biocatalysts

bout acib

ontact

Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions for chemical problems - Enzyme Engineering & Technology - eynzmes designed for industry - Biocatalytic Synthesis - enzymatic solutions

Reduction of Carboxylic Acids

(CAR = carboxylate reductase, ADH = alcohol dehydrogenase; ChemCatChem 2014, 6, 1089-1095; Biotechnol. J. 2014, 9, 822-843; Chemical Monthly, 2016, 147, 575-578; Adv. Synth. Catal., 2016, in press, DOI: 10.1002/adsc.201600914.)

Reductive Biotransformations

Reduction of Aldehydes and Ketones

(ADH = alcohol dehydrogenase; Angew. Chem., Int. Ed. 2002, 41, 1014; Angew. Chem., Int. Ed. 2008, 47, 714; ChemCatChem 2013, 5, 1744.)

Reduction of C=C-Bonds

(X = electron-withdrawing group; Angew. Chem., Int. Ed. 2007, 46, 3934; Chem. Eur. J. 2012, 18, 10367; Curr. Opin. Chem. Biol. 2007, 11, 203; J. Biotechnol. 2012, 162, 381; Nat. Commun. 2014, 5, 4150.)

Reduction of Imines

(IRED = imine reductase; Adv. Synth. Catal. 2015, 357, 1655.)


Reductive BiotransformationsReductive Amination of Aldehydes and Ketones

(TA = ω-transaminase; Angew. Chem., Int. Ed. 2008, 47, 9337; Angew. Chem., Int. Ed. 2012, 27, 1; Org. Process Res. Dev. 2013, 17, 751; ACS Catal. 2014, 4, 129.)

Structure of an Ene- eductase


Oxidation of Alcohols / Aldehydes

(ADH = alcohol dehydrogenase; Angew. Chem., Int. Ed. 2002, 41, 1014; Angew. Chem., Int. Ed. 2008, 47, 714; J. Am. Chem. Soc. 2008, 130, 13969; ChemCatChem 2013, 5, 1744.)

C=C-Bond Cleavage

(Angew. Chem., Int. Ed. 2006, 45, 5201; J. Am. Chem. Soc. 2009, 131, 5368; Chem. Commun. 2012, 48, 3303; Adv. Synth. Catal. 2013, 355, 3321.)

Enzymatic De-Amination

(TA = ω-transaminase; AO = α-amino oxidase; Angew. Chem., Int. Ed. 2008, 47, 9337; Angew. Chem., Int. Ed. 2012, 27, 6817; Org. Process Res. Dev. 2013, 17, 751; ACS Catal. 2014, 4, 129.)

Enzymatic De-Alkylation

Oxidative Biotransformations

Enzymatic Hydration

(Angew. Chem. Int. Ed. 2015, 54, 15051.)

(Angew. Chem., Int. Ed. 2013, 52, 2293.)


Oxidative Biotransformations

Enzymatic Hydroxylation

(Nat. Biotechnol. 2002, 20, 1135.)

Baeyer-Villiger Oxidation

(hFMO = human flavin containing monooxygenase; ACS Chem. Biol., 2016, 11, 1039-1048.)

Oxyfunctionalisation of Amino Acids

Oxidative Decarboxylation

(Angew. Chem. Int. Ed. 2015, 54, 8819–8822; Chem. Commun., 2016, 51, 1918; Eur. J. Org. Chem., 2016, 2473–3477.)

(aKG = a-ketoglutarate; AAD = amino acid dioxygenase; Front. Microbiol., 2016, 7, 425.)


Bio-Carboxylation

(Chem. Soc. Rev. 2010, 39, 313; Org. Lett. 2012, 14, 1974; J. Biotechnol. 2013, 168, 264; RSC Adv. 2014, 4, 9673.)

Bio-Friedel-Crafts Acylation

(unpublished results)

Biocatalytic Alkaloid Synthesis

(BBE = berberine bridge enzyme; STR = stricto-sidine synthase; NCS = norcoclaurine synthase; Angew. Chem., Int. Ed. 2011, 50, 1068; Org. Pro-cess Res. Dev. 2013, 17, 751; Angew. Chem., Int. Ed. 2014, 53, 3731.)

Trifluoromethylation

(TFMS = trifluoromethylsulfonic acid; TBHP = tert-butylhydroperoxide; Nat. Commun. 2016, in press, DOI: 10.1038/ncomms13323.)

C-C Bond Formation


Cyanohydrin Synthesis/Henry Reaction

(HNL = hydroxynitrile lyase; Angew. Chem., Int. Ed. 2006, 45, 3454; Adv. Synth. Catal. 2007, 349, 1445; ChemCat-Chem 2015, 7, 325; Angew. Chem., Int. Ed. 2003, 42, 4815; Curr. Biotechnol., 2015, 4, 111-117.)

C-C Bond Formation

Asymmetric Synthesis of Optically Pure α-Substituted Carboxylic Acids

(AMDase = arylmalonate decarboxylase; ChemCatChem, 2016, 8, 916; Appl. Microbiol. Biotechnol., 2016, 20, 8621.)

C-C Bond Breaking


Racemization of Arylpropionates

(APR = arylpropionate racemase; ChemBioChem, 2016, 16, 1943; Cat. Sci. Technol., 2016, 6, 4397.)

Enzymatic Isomerisation

Isomerisations of C=C-Bonds

(ChemBioChem, 2012, 13, 2346–2351.)

Disproportionation: Biocatalytic Cannizzaro Reaction

(ADH = alcohol dehydrogenase; ChemCatChem, 2013, 5, 1744–1748.)


Hydrolysis of Lactams

(ChemCatChem 2014, 6, 2517.)

Bio-Mitsunobu-Inversion

(Angew. Chem., Int. Ed. 2002, 41, 1014; Angew. Chem., Int. Ed. 2005, 44, 6381; Angew. Chem., Int. Ed. 2013, 52, 3277; Eur. J. Org. Chem. 2013, 356; Trends Biotechnol. 2013, 31, 468; Appl. Microbiol. Biotechnol. 2014, 4, 1485.)

C-C Bond Hydrolysis

(Adv. Synth. Catal. 2013, 355, 1677; Adv. Synth. Catal. 2013, 355, 1703; Top. Catal. 2014, 57, 376.)

Hydrolysis / Esterification

Nitrile Hydrolysis

(Tetrahedron 2005, 61, 4249-4260; ChemCatChem 2010, 2, 267-269; Enz. Microb. Technol. 2010, 47, 140-146; OBC 2015, 13, 7803-7812.)


Enantioselective Ester Formation in Aqueous Systems

(AT= acyl transferase; to be published.)

Hydrolysis / Esterification

Enzymatic Phosphorylation

(PPi = phyrophosphate; Eur. J. Org. Chem., 2016, 45–50.)

Chemoenzymatic Preparation of Bio-Based Anti-Oxidants

(PAD = phenolic acid decarboxylase; Angew. Chem., Int. Ed., 2016, in press, DOI: 10.1002/anie.201607777.)

Enzymatic Cascades


Direct Amination of Alcohols

(ADH = alcohol dehydrogenase; TA = ω-transaminase; Angew. Chem., Int. Ed. 2012, 51, 9156; ACS Catal. 2014, 4, 129.)

6-Aminohexanoic Acid from Cyclohexanol

(ADH = alcohol dehydrogenase; BVMO = Baeyer-Villiger monooxygenase, TA = ω-transaminase; Angew. Chem., Int. Ed. 2014, 53, 14153; ACS Catal. 2014, 4, 129.)

Cyclohexylamines from Diketones

(TA = ω-transaminase; Adv. Synth. Catal. 2013, 355, 1703.)

Vinylation of Phenols

(Angew. Chem. Int. Ed. 2015, 45, 10899.)

Enzymatic Cascades


Regioselective Glycosyltransfer

(Biocat. Biotrans. 2010, 28, 10; Pure Appl. Chem. 2013, 85, 1865; PCT Int. Appl. 2015, WO 2015001033.)

Small Molecule Glycosylation

(Angew. Chem., Int. Ed. 2008, 47, 10086; PCT Int. Appl. 2008, WO 2008034158.)

Regioselective Glucosylation – Flavonoid Glycosylation

(Green Chem. 2014, 16, 4417.)

Glycozyme Technology


Nucleotid Sugar Synthesis

(SPase = sucrose phosphorylase; AGP = α-D-glucose 1-phosphate phosphatase; PPase = pyrophosphatase; NTPase = nucleotide transferase; GTP = guanosine 5′-triphosphate; D-Glc = D-glucose; D-Fru = D-fructose; Pi = inorganic phosphate; Adv. Synth. Catal., submitted.)

Glycozyme Technology

Diasterioselecitve Synthesis of Glycosyl Phosphates

(SPase = sucrose phosphorylase; AGP = α -D-glucose 1-phosphate phosphatase; D-Glc = D-glucose; D-Fru = D-fructose; Pi = inorganic phosphate; Angew. Chem.,Int. Ed., 2015, 54,15867.)


Chemo- & Regioselective Oxidation of Soft Nucleophiles

(Chem. Commun. 2012, 48, 6001-6003; ChemCatChem 2014, 6, 1028-1042; Microb. Cell Fact. 2015, 14:82, 1-10; J. Biotechnol. 2016, 235, 3.)

API-Modification with Human Enzymes


In-silico Search for Novel BiocatalystsTraditional screening for no el enzymes re uires time-consuming e periments and e pensi e acti ity assays in the et-lab To reduce costs the prediction and identi cation of enzyme func-tionalities is a ma or challenge of modern bioinformatics o e er the computational annota-tion of proteins pro es to be di cult erroneous and lac s the possibility to identify completely independent no el biocatalysts because they rely on the correlation of se uence similarities

ith the no n functions of the template and are bound to nd more of the same

Catalophore Search for Novel Enzymes

acib-researchers de eloped a patented bioinformatics method1 to mine structural databases using three dimensional search templates hich co er the arrangement of chemical functio-nal groups or pre-calculated point-clouds representing the empty space of acti e sites These search templates are termed catalophores i e carrier of the catalytic function The searches are independent of structural or se uence similarities to currently employed enzymes Therefo-re these identi ed enzymes may feature di erent physico-chemical properties such as stability selecti ity or substrate tolerance

successful test-case led to the identi cation of t o no el ene-reductases2 by searching ith pa erns obtained from classical old yello enzymes The identi ed enzymes sho ed signi cant con ersions on typical old yello enzyme substrates and e en allo ed access to enantiomers that could not be obtained using current enzyme por olio although the o erall se uence and structural similarity are belo

atalophore used for the identi cation of the old-yello enzyme e ample a schematic mechanism of the reaction mechanism b acti e site constella-tion catalphore c catalophore mo-tif indicating used atom types d geo-metrical representation of the search motif used for the database search

(1. PCT/EP2013/074556, 2014, ACIB GmbH and University of Graz; 2. Nat. Commun. 2014, 5, 4150.)


next step in industrial research

The ustrian entre of ndustrial Biotechnology acib is an international research center ith employees based in ustria ith ith collaborati e lin s to ermany Slo enia taly Spain and oland acib can dra on ye-ars of e perience to apply sophisticated ne methods in industrial production focused on biocatalysis enzymes polymers pharmaceutical protein production & puri ca-tion cell line de elopment bioinformatics and synthetic biology

Together ith industrial and scienti c partners acib adopts the tools and methods of nature for i ne produc-tion processes & products ith impro ed ecological e ci-ency ii ne production processes ith higher economic e ciency iii products ith higher uality and purity i functional inno ati e products for e eryday use and sophisticated computational methods for the health care pharmaceutical or chemical industry

acib science ist our success

about acib

The competence centre acib is funded in the frame or of ET ompetence enters for E cellent Technologies by B T B and the pro inces of o er

ustria Styria Tyrol and ienna The ET programme is conducted by


acib at biocatalysis uni-graz at

ing com companies acibgmbhlin edin com company acib-gmbhfaceboo com acibgmbh

contact

Dr. Martin Trinker

esearch anagementBusiness e elopment

t fa m martin trin er acib at

acib mbaustrian centre of industrial biotechnology

etersgasse raz

ustria

Prof. Kurt Faber

t m urt faber uni-graz at

Prof. Wolfgang Kroutil

t m olfgang routil uni-graz at

Dr. Christoph Winkler

t m christoph in ler uni-graz at

acib mbc o epartment of hemistry ni ersity of raz

razustria


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Enzyme Engineering & Technology - acib