Syed Ahmed

The University of Manchester · Manchester Institute of Biotechnology

Terpenes are the largest class of natural products with extensive structural diversity and are widely used as pharmaceuticals, herbicides, flavourings, fragrances, and biofuels. While they have mostly been isolated from plants and fungi, the availability and analysis of bacterial genome sequence data indicates that bacteria also possess many putati...

The conversion of carboxylic acids, such as acrylic acids, to amines is a transformation that remains challenging in synthetic organic chemistry. Despite the ubiquity of similar moieties in natural metabolic pathways, biocatalytic routes seem to have been overlooked for this purpose. Herein we present the conception and optimisation of a two‐enzyme...

Advancements in directed evolution and genome sequencing have led to the discovery and evolution of enzymes with new and improved catalytic properties. The pharmaceutical industry has greatly benefited from this, evidenced by the number of publications and manufacturing processes reported in the last decade. However, biocatalysts are rarely reporte...

Monoterpenoids offer potential as bio-derived monomer feedstocks for high performance renewable polymers. We describe a biocatalytic route to lactone monomers menthide and dihydrocarvide employing Baeyer-Villiger monooxygenases (BVMOs) from Pseudomonas sp. HI-70 (CPDMO) and Rhodococcus sp. Phi1 (CHMOPhi1) as an alternative to organic synthesis. The...

Engineered variants of phenylalanine ammonia lyase from Planctomyces brasiliensis were developed through rational design efforts focusing on the aryl binding pocket of the active site, guided by structural and phylogenetic inference. Inherent problems traditionally associated with the biocatalytic hydroamination of acrylic acids, such as low conver...

The effect of extended reaction times on the regio- and enantioselectivity of the phenylalanine ammonia lyase (PAL)-catalysed amination of a subset of cinnamate derivatives was investigated. This was done using a PAL from the cyanobacterium Anabaena variabilis and incubation in a concentrated ammonia buffer. Whilst early time point analyses reveale...

The suite of biological catalysts found in Nature has the potential to contribute immensely to scientific advancements, ranging from industrial biotechnology to innovations in bioenergy and medical intervention. The endeavour to obtain a catalyst of choice is, however, wrought with challenges. Herein we report the design of a structure-based annota...

Phenylalanine ammonia lyase has played a key role in the sustainable production of non-natural amino acids as chiral building blocks for pharmaceutical applications, as demonstrated, for instance, by the production of (S)-2-indolinecarboxylic acid by DSM. In recent years, the cyanobacterial PAL from Anabaena variabilis has been shown to be a robust...

Ammonia-lyases and aminomutases are mechanistically and structurally diverse enzymes which catalyze the deamination and/or isomerization of amino acids in nature by cleaving or shifting a C-N bond. Of the many protein families in which these enzyme activities are found, only a subset have been employed in the synthesis of optically pure fine chemic...

Reduction of double bonds of α,β-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow En...

An enzymatic strategy for the preparation of ( R )‐β‐arylalanines employing phenylalanine aminomutase and ammonia lyase (PAM and PAL) enzymes has been demonstrated. Candidate PAMs with the desired ( S )‐selectivity from Streptomyces maritimus (EncP) and Bacillus sp. (PabH) were identified via sequence analysis using a well‐studied template sequence...

Current routes to nitrogen-containing heteroarylalanines involve complex multistep synthesis and are often reliant on protection/deprotection steps and wasteful chromatographic purifications. In order to complement existing methodologies, a convenient telescopic strategy was developed for the synthesis of l-pyridylalanine analogues (12 examples) an...

A practical and efficient biocatalytic synthesis of aromatic d ‐amino acids has been developed, based on the reductive amination of the corresponding α‐keto acids via a recombinant whole cell system composed of an engineered dehydrogenase and cofactor recycling apparatus. The reaction was shown to give excellent enantioselectivity (≥98%) and good y...

An intensified, industrially-relevant strategy for the production of enantiopure halophenylalanines has been developed using the novel combination of a cyanobacterial phenylalanine ammonia lyase (PAL) and ammonium carbamate reaction buffer. The process boasts STYs up to >200 g L-1 d-1, ees ≥ 98% and simplified catalyst/reaction buffer preparation a...

Biocatalysts are increasingly used by chemists engaged in fine chemical synthesis within both industry and academia. Today, there exists a huge choice of high-tech enzymes and whole cell biocatalysts, which add enormously to the repertoire of synthetic possibilities. Practical Methods for Biocatalysis and Biotransformations 3 will be a companion b...

A chemo-enzymatic telescopic approach was designed for the synthesis of L-arylalanines in high yield and optical purity, starting from commercially available and inexpensive substituted benzaldehydes. The method exploits a chemical Knoevenagel–Doebner condensation (optimised to give complete conversions in a short reaction time, employing microwave...

Enzymes of the class I lyase-like family catalyze the asymmetric addition of ammonia to arylacrylates, yielding high value amino acids as products. Recent examples include the use of phenylalanine ammonia lyases (PALs), either alone or as a gateway to deracemization cascades (giving (S)- or (R)-α-phenylalanine derivatives respectively), and also eu...

A chemoenzymatic approach was developed and optimized for the synthesis of a range of N-protected nonnatural l- and d-biarylalanine derivatives. Starting from 4-bromocinnamic acid and 4-bromophenylpyruvic acid using a phenylalanine ammonia lyase (PAL) and an evolved d-amino acid dehydrogenase (DAADH), respectively, both enantiomers of 4-bromophenyl...

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The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple hig...

The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple hig...

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