Journal
CHEMBIOCHEM
Volume 22, Issue 13, Pages 2262-2265Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202100145
Keywords
Biocatalysis; Indole; Nitration; Protein Engineering
Funding
- BBSRC [BB/L502017/1, BB/K002341/1]
- GlaxoSmithKline
- BBSRC [BB/K002341/1, BB/L502017/1] Funding Source: UKRI
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The variant R59C of TxtE has a broader substrate scope, allowing it to nitrate a range of tryptamine analogues. This presents a new direction for developing TxtE into a useful aromatic nitration biocatalyst.
Aromatic nitration reactions are a cornerstone of organic chemistry, but are challenging to scale due to corrosive reagents and elevated temperatures. The cytochrome P450 TxtE nitrates the indole 4-position of l-tryptophan at room temperature using NO, O-2 and NADPH, and has potential to be developed into a useful aromatic nitration biocatalyst. However, its narrow substrate scope (requiring both the alpha-amino acid and indole functionalities) have hindered this. Screening of an R59 mutant library of a TxtE-reductase fusion protein identified a variant (R59C) that nitrates tryptamine, which is not accepted by native TxtE. This variant exhibits a broader substrate scope than the wild type enzyme and is able to nitrate a range of tryptamine analogues, with significant alterations to the aromatic and aminoethyl moieties.
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