<i>N</i>-Phenylputrescine (NPP): a natural product inspired amine donor for biocatalysis

McKenna, Catherine A; Štiblariková, Mária; Silvestro, Irene De; Campopiano, Dominic J.; Lawrence, Andrew L.

doi:10.1039/d1gc02387j

Cited by 13 publications

(19 citation statements)

References 45 publications

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“…N -phenylputrescine was designed to mimic the native donor used in the incargranine B biosynthetic pathway, rendering the reaction with this donor irreversible . Minimal activity was observed in the NPP screen apart from substrates H and I .…”

Section: Resultsmentioning

confidence: 99%

Comparison of Diverse Amine Donors for Use in the High-Throughput Screening of Amine Transaminases

Brown

Phelan

2023

Org. Process Res. Dev.

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Chiral amines are important structural features of many pharmaceutical and agrochemical compounds; accordingly, numerous synthetic methods have been developed to enable the installation of this functional group. Of the many available methods, amine transaminases have gained attention as stereoselective, efficient, and green catalysts. As selection of transaminases for a given transformation most often cannot be performed a priori, high-throughput screens are often used to identify a suitable catalyst. One concern with high-throughput screening is that while the transaminase may accept a particular substrate, it is possible that the amine donor may not be compatible with the enzyme in question. Here, we compare five common and diverse amine donors and identify those that have the broadest compatibility with various amine transaminases. Findings were used to further probe larger enzyme panels and reveal preferences that engineered and wild-type enzymes have for differing amine donors. In the process of exploring amine donors, we also define a concise set of transaminases that catalyze the production of substituted benzylamines.

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Section: Resultsmentioning

confidence: 99%

Comparison of Diverse Amine Donors for Use in the High-Throughput Screening of Amine Transaminases

Brown

Phelan

2023

Org. Process Res. Dev.

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“…The preferred amine donor was found to be l -Glu (but it can also accept l -Ala to a lesser extent), and it also displays a broad substrate promiscuity by being able to accept C 7 –C 14 aldehydes. In future, the synthetic utility of this TA could be further expanded by studying its activity with smart amine donors such as cadaverine, o -xylylenediamine, and N -phenylputrescine (NPP). − …”

Section: Discussionmentioning

confidence: 99%

“…In future, the synthetic utility of this TA could be further expanded by studying its activity with smart amine donors such as cadaverine, o -xylylenediamine, and N -phenylputrescine (NPP). 53 − 55 …”

Section: Discussionmentioning

confidence: 99%

Coupled Natural Fusion Enzymes in a Novel Biocatalytic Cascade Convert Fatty Acids to Amines

et al. 2022

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Tambjamine YP1 is a pyrrole-containing natural product. Analysis of the enzymes encoded in the Pseudoalteromonas tunicata “tam” biosynthetic gene cluster (BGC) identified a unique di-domain biocatalyst (PtTamH). Sequence and bioinformatic analysis predicts that PtTamH comprises an N-terminal, pyridoxal 5′-phosphate (PLP)-dependent transaminase (TA) domain fused to a NADH-dependent C-terminal thioester reductase (TR) domain. Spectroscopic and chemical analysis revealed that the TA domain binds PLP, utilizes l-Glu as an amine donor, accepts a range of fatty aldehydes (C7–C14 with a preference for C12), and produces the corresponding amines. The previously characterized PtTamA from the “tam” BGC is an ATP-dependent, di-domain enzyme comprising a class I adenylation domain fused to an acyl carrier protein (ACP). Since recombinant PtTamA catalyzes the activation and thioesterification of C12 acid to the holo-ACP domain, we hypothesized that C12 ACP is the natural substrate for PtTamH. PtTamA and PtTamH were successfully coupled together in a biocatalytic cascade that converts fatty acids (FAs) to amines in one pot. Moreover, a structural model of PtTamH provides insights into how the TA and TR domains are organized. This work not only characterizes the formation of the tambjamine YP1 tail but also suggests that PtTamA and PtTamH could be useful biocatalysts for FA to amine functional group conversion.

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“…7 TAs are useful biocatalysts but suffer from the problem of reversibility of the amine transfer step. 8 An alternative route to the α-aminoketone building block would be to use a different PLP-dependent biocatalyst that does not rely on reversible amine transfer. α-Oxoamine synthases (AOS) fall within this category.…”

mentioning

confidence: 99%

“…A similar TA-mediated amine borrowing strategy, coupled with a KPR, was recently used to generate a small library of pyrroles . TAs are useful biocatalysts but suffer from the problem of reversibility of the amine transfer step …”

mentioning

confidence: 99%

Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

Ashley,

Baslé,

Sajjad

et al. 2023

ACS Sustainable Chem. Eng.

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We report a chemo-biocatalytic cascade for the synthesis of substituted pyrroles, driven by the action of an irreversible, thermostable, pyridoxal 5′-phosphate (PLP)-dependent, C–C bond-forming biocatalyst (ThAOS). The ThAOS catalyzes the Claisen-like condensation between various amino acids and acyl-CoA substrates to generate a range of α-aminoketones. These products are reacted with β-keto esters in an irreversible Knorr pyrrole reaction. The determination of the 1.6 Å resolution crystal structure of the PLP-bound form of ThAOS lays the foundation for future engineering and directed evolution. This report establishes the AOS family as useful and versatile C–C bond-forming biocatalysts.

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N-Phenylputrescine (NPP): a natural product inspired amine donor for biocatalysis

Abstract: The synthesis of chiral amines in enantioenriched form is a keystone reaction in applied chemical synthesis. There is a strong push to develop greener and more sustainable alternatives to the...

Cited by 13 publications

References 45 publications

Comparison of Diverse Amine Donors for Use in the High-Throughput Screening of Amine Transaminases

Comparison of Diverse Amine Donors for Use in the High-Throughput Screening of Amine Transaminases

Coupled Natural Fusion Enzymes in a Novel Biocatalytic Cascade Convert Fatty Acids to Amines

Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

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