Directed Evolution of a Halide Methyltransferase Enables Biocatalytic Synthesis of Diverse SAM Analogs

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(3), P. 1524 - 1527

Published: Oct. 27, 2020

Abstract Biocatalytic alkylations are important reactions to obtain chemo‐, regio‐ and stereoselectively alkylated compounds. This can be achieved using S‐adenosyl‐ l ‐methionine (SAM)‐dependent methyltransferases SAM analogs. It was recently shown that a halide methyltransferase (HMT) from Chloracidobacterium thermophilum synthesize SAH methyl iodide. We developed an iodide‐based assay for the directed evolution of HMT Arabidopsis thaliana used it identify V140T variant also accept ethyl‐, propyl‐, allyl iodide produce corresponding analogs (90, 50, 70 % conversion 15 mg SAH). The AtHMT in one‐pot cascades with O ‐methyltransferases (IeOMT or COMT) achieve regioselective ethylation luteolin allylation 3,4‐dihydroxybenzaldehyde. While cascade propylation 3,4‐dihydroxybenzaldehyde gave low conversion, propyl‐SAH intermediate could confirmed by NMR spectroscopy.

Language: Английский

---

Applications of endophytic microbes in agriculture, biotechnology, medicine, and beyond

Microbiological Research, Journal Year: 2021, Volume and Issue: 245, P. 126691 - 126691

Published: Jan. 13, 2021

Language: Английский

---

Streamlining Design, Engineering, and Applications of Enzymes for Sustainable Biocatalysis

ACS Sustainable Chemistry & Engineering, Journal Year: 2021, Volume and Issue: 9(24), P. 8032 - 8052

Published: June 9, 2021

In this Perspective we show how an expansion of the scope and impact biocatalysis in industrial organic synthesis is enabled by streamlining underpinning biocatalyst bioprocess engineering. We begin discussing underlying need for waste reduction high (enantio)selectivities fostered introduction as a sustainable technology active pharmaceutical ingredients (APIs). continue showing advances molecular biology, particular gene sequencing protein engineering, development more better enzymes, thereby broadening biocatalysis. Further process improvements are provided through engineering enzyme immobilization integration production with vivo immobilization. Finally, use immobilized enzymes continuous operation (biocatalysis flow) facilitates sequential multi-step reactions into enzymatic or chemo-enzymatic cascade processes, thus enabling complete, cost-effective, environmentally attractive APIs.

Language: Английский

---

Chemoenzymatic Total Synthesis of Natural Products

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(6), P. 1374 - 1384

Published: Feb. 18, 2021

The total synthesis of structurally complex natural products has challenged and inspired generations chemists remains an exciting area active research. Despite their history as privileged bioactivity-rich scaffolds, the use in drug discovery waned. This shift is driven by relatively low abundance hindering isolation from sources challenges presented synthesis. Recent developments biocatalysis have resulted application enzymes for construction molecules. From inception Narayan lab 2015, we focused on harnessing exquisite selectivity alongside contemporary small molecule-based approaches to enable concise chemoenzymatic routes products.We various families that perform selective oxidation reactions. For example, targeted xyloketal through a strategy relies chemo- site-selective biocatalytic hydroxylation. Members family are characterized polycyclic ketal cores demonstrate potent neurological activity. We envisioned assembling representative product (xyloketal D) involving biocatalytically generated

Language: Английский

---

Taguchi design-assisted co-immobilization of lipase A and B from Candida antarctica onto chitosan: Characterization, kinetic resolution application, and docking studies

Process Safety and Environmental Protection, Journal Year: 2021, Volume and Issue: 177, P. 223 - 244

Published: Oct. 29, 2021

Language: Английский

---