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Exploring water as building bricks in enzyme engineering
KTH, Skolan för bioteknologi (BIO), Industriell bioteknologi.ORCID-id: 0000-0001-9001-9271
KTH, Skolan för bioteknologi (BIO), Industriell bioteknologi.ORCID-id: 0000-0002-2993-9375
KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.ORCID-id: 0000-0002-4066-2776
2015 (engelsk)Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 51, nr 97, s. 17221-17224Artikkel i tidsskrift (Fagfellevurdert) Published
Resurstyp
Text
Abstract [en]

A novel enzyme engineering strategy for accelerated catalysis based on redesigning a water network through protein backbone deshielding is presented. Fundamental insight into the energetic consequences associated with the design is discussed in the light of experimental results and computer simulations. Using water as biobricks provides unique opportunities when transition state stabilisation is not easily attained by traditional enzyme engineering.

sted, utgiver, år, opplag, sider
Royal Society of Chemistry, 2015. Vol. 51, nr 97, s. 17221-17224
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-180600DOI: 10.1039/c5cc07162cISI: 000366954800004PubMedID: 26426706Scopus ID: 2-s2.0-84948408732OAI: oai:DiVA.org:kth-180600DiVA, id: diva2:896177
Forskningsfinansiär
Swedish Research Council, 621-2013-5138
Merknad

QC 20160120

Tilgjengelig fra: 2016-01-20 Laget: 2016-01-19 Sist oppdatert: 2017-11-30bibliografisk kontrollert
Inngår i avhandling
1. Rational engineering of esterases for improved amidase specificity in amide synthesis and hydrolysis
Åpne denne publikasjonen i ny fane eller vindu >>Rational engineering of esterases for improved amidase specificity in amide synthesis and hydrolysis
2016 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Biocatalysis is an ever evolving field that uses enzymes or microorganisms for chemical synthesis. By utilizing enzymes that generally have evolved for specific reactions under mild conditions and temperatures, biocatalysis can be a more environmentally friendly option compared to traditional chemistry.

Amide-type chemistries are important and bond formation avoiding poor atom economy is of high priority in organic chemistry. Biocatalysis could potentially be a solution but restricted substrate scope is a limitation. Esterases/lipases usually display broad substrate scope and catalytic promiscuity but are poor at hydrolyzing amides compared to amidases/proteases. The difference between the two enzyme classes is hypothesized to reside in one key hydrogen bond present in amidases, which facilitates the transition state for nitrogen inversion during catalysis.

In this thesis the work has been focused on introducing a stabilizing hydrogen bond acceptor in esterases, mimicking that found in amidases, to develop better enzymatic catalysts for amide-based chemistries.

By two strategies, side-chain or water interaction, variants were created in three esterases that displayed up to 210-times increased relative amidase specificity compared to the wild type. The best variant displayed reduced activation enthalpy corresponding to a weak hydrogen bond. The results show an estimated lower limit on how much the hydrogen bond can be worth to catalysis.

MsAcT catalyze kinetically controlled N-acylations in water. An enzymatic one-pot one-step cascade was developed for the formation of amides from aldehydes in water that gave 97% conversion. In addition, engineered variants of MsAcT with increased substrate scope could synthesize an amide in water with 81% conversion, where the wild type gave no conversion. Moreover, variants of MsAcT displayed up to 32-fold change in specificity towards amide synthesis and a switch in reaction preference favoring amide over ester synthesis.

sted, utgiver, år, opplag, sider
Stockholm: KTH Royal Institute of Technology, 2016. s. 76
Serie
TRITA-BIO-Report, ISSN 1654-2312 ; 2016:21
Emneord
Amidase, Biocatalysis, Enzyme, Esterase, Enzyme engineering, Lipase, Substrate specificity
HSV kategori
Forskningsprogram
Bioteknologi
Identifikatorer
urn:nbn:se:kth:diva-196892 (URN)978-91-7729-210-4 (ISBN)
Disputas
2016-12-16, FD5, AlbaNova University Center, Roslagstullsbacken 21, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad

QC 20161125

Tilgjengelig fra: 2016-11-25 Laget: 2016-11-24 Sist oppdatert: 2016-11-25bibliografisk kontrollert

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