Details
| Original language | English |
|---|---|
| Pages (from-to) | 49987-49995 |
| Number of pages | 9 |
| Journal | RSC Advances |
| Volume | 5 |
| Issue number | 62 |
| Publication status | Published - 1 Jan 2015 |
Abstract
Achieving regio-specific hydroxylation of aromatic compounds remains a major challenge in synthetic chemistry. By contrast, this transformation is readily accomplished in nature through the action of FAD-dependant monooxygenase enzymes. Here, we report the kinetic characterisation of one such enzyme, TropB, from the stipitatic acid biosynthetic pathway. Analogues of the TropB natural substrate, 3-methyl-orcinaldehyde, were synthesised and used to examine the substrate selectivity of this enzyme. TropB displays broad substrate tolerance, for instance accepting single-ring aromatic substrates containing a range of C-1 substituents with varying electronic and steric properties. These include nitro, nitrosyl, alkyl, and aryl keto groups. Bicyclic substrates, however, were rejected by TropB. Additionally, C-5 substituents on single-ring aromatic substrates were not tolerated whereas the presence of a 6-methyl group was found to be important for substrate binding. Docking studies were employed to investigate and understand the broad substrate selectivity of TropB and identifies the key structural elements of its substrates. Our work has shown that TropB is an attractive target for biocatalyst engineering and industrial aromatic hydroxylation.
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
- Chemical Engineering(all)
- General Chemical Engineering
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In: RSC Advances, Vol. 5, No. 62, 01.01.2015, p. 49987-49995.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Kinetic characterisation of the FAD dependent monooxygenase TropB and investigation of its biotransformation potential
AU - Abood, Amira
AU - Al-Fahad, Ahmed
AU - Scott, Alan
AU - Hosny, Alaa El Dein M.S.
AU - Hashem, Amal M.
AU - Fattah, Azza M.A.
AU - Race, Paul R.
AU - Simpson, Thomas J.
AU - Cox, Russell J.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Achieving regio-specific hydroxylation of aromatic compounds remains a major challenge in synthetic chemistry. By contrast, this transformation is readily accomplished in nature through the action of FAD-dependant monooxygenase enzymes. Here, we report the kinetic characterisation of one such enzyme, TropB, from the stipitatic acid biosynthetic pathway. Analogues of the TropB natural substrate, 3-methyl-orcinaldehyde, were synthesised and used to examine the substrate selectivity of this enzyme. TropB displays broad substrate tolerance, for instance accepting single-ring aromatic substrates containing a range of C-1 substituents with varying electronic and steric properties. These include nitro, nitrosyl, alkyl, and aryl keto groups. Bicyclic substrates, however, were rejected by TropB. Additionally, C-5 substituents on single-ring aromatic substrates were not tolerated whereas the presence of a 6-methyl group was found to be important for substrate binding. Docking studies were employed to investigate and understand the broad substrate selectivity of TropB and identifies the key structural elements of its substrates. Our work has shown that TropB is an attractive target for biocatalyst engineering and industrial aromatic hydroxylation.
AB - Achieving regio-specific hydroxylation of aromatic compounds remains a major challenge in synthetic chemistry. By contrast, this transformation is readily accomplished in nature through the action of FAD-dependant monooxygenase enzymes. Here, we report the kinetic characterisation of one such enzyme, TropB, from the stipitatic acid biosynthetic pathway. Analogues of the TropB natural substrate, 3-methyl-orcinaldehyde, were synthesised and used to examine the substrate selectivity of this enzyme. TropB displays broad substrate tolerance, for instance accepting single-ring aromatic substrates containing a range of C-1 substituents with varying electronic and steric properties. These include nitro, nitrosyl, alkyl, and aryl keto groups. Bicyclic substrates, however, were rejected by TropB. Additionally, C-5 substituents on single-ring aromatic substrates were not tolerated whereas the presence of a 6-methyl group was found to be important for substrate binding. Docking studies were employed to investigate and understand the broad substrate selectivity of TropB and identifies the key structural elements of its substrates. Our work has shown that TropB is an attractive target for biocatalyst engineering and industrial aromatic hydroxylation.
UR - http://www.scopus.com/inward/record.url?scp=84935921571&partnerID=8YFLogxK
U2 - 10.1039/c5ra06693j
DO - 10.1039/c5ra06693j
M3 - Article
AN - SCOPUS:84935921571
VL - 5
SP - 49987
EP - 49995
JO - RSC Advances
JF - RSC Advances
SN - 2046-2069
IS - 62
ER -