Microbial soluble aromatic prenyltransferases for engineered biosynthesis

Chen, He‐Ping; Abe, Ikuro

doi:10.1016/j.synbio.2021.02.001

Cited by 13 publications

(14 citation statements)

References 50 publications

(38 reference statements)

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“…Aromatic prenyltransferases catalyze regioselective Friedel-Crafts alkylations of aromatic acceptor molecules with diverse isoprenoid diphosphates (Chen and Abe 2021 ). Not only are these enzymes involved in the biosynthesis of several bioactive natural products, but also some of their members have been identified as versatile biocatalysts in terms of substrate tolerance and in their ability to form carbon-carbon as well as carbon-heteroatom bonds (Winkelblech et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Biocatalytic production of the antibiotic aurachin D in Escherichia coli

2022

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Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with recombinant Escherichia coli cells expressing the biosynthesis enzyme AuaA. In order to achieve a high-level production of this membrane-bound farnesyltransferase in E. coli, the expression of the auaA gene was translationally coupled to an upstream cistron in accordance with a bicistronic design (BCD) strategy. Screening of various BCD elements led to the identification of optimized auaA expression cassettes, which increased the aurachin D titer in E. coli up to 29-fold in comparison to T7-mediated expression. This titer could be further raised by codon optimization of auaA and by introducing the mevalonate pathway into the production strain. The latter measure was intended to improve the availability of farnesyl pyrophosphate, which is needed as a cosubstrate for the AuaA-catalyzed reaction. In sum, the described efforts resulted in a strain producing aurachin D with a titer that is 424 times higher than that obtained with the original, non-optimized expression host. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Biocatalytic production of the antibiotic aurachin D in Escherichia coli

2022

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“… [45] This broad enzyme family is often divided into three categories: Mg 2+ ‐dependent membrane‐bound UbiA‐type enzymes, dimethylallyltryptophan synthase (DMATS)‐type enzymes, and ABBA‐type enzymes. [46] The first type are found in bacteria, plants and fungi and contain an aspartate‐rich motif for metal‐ion binding, whilst the latter two types are not found in plants, and contain no metal‐binding motif.…”

Section: Aromatic Prenyl‐transferases (Aptases)mentioning

confidence: 99%

“… [67] The discussion on this diverse enzyme family provided here is far from exhaustive, and for further information we direct the reader to recent reviews on the topic. [ 46 , 68 ] The broad range of aromatic substrates identified with various aPTases, as well as their frequent acceptance of alternative and non‐natural prenyl‐donors, makes them appealing biocatalysts for the preparation of many alkyl‐aryl linkages.…”

Section: Aromatic Prenyl‐transferases (Aptases)mentioning

confidence: 99%

Biocatalytic Friedel‐Crafts Reactions

Leveson-Gower

Roelfes

2022

ChemCatChem

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Friedel-Crafts alkylation and acylation reactions are important methodologies in synthetic and industrial chemistry for the construction of aryl-alkyl and aryl-acyl linkages that are ubiquitous in bioactive molecules. Nature also exploits these reactions in many biosynthetic processes. Much work has been done to expand the synthetic application of these enzymes to unnatural substrates through directed evolution. The promise of such biocatalysts is their potential to supersede inefficient and toxic chemical approaches to these reactions, with mild operating conditions -the hallmark of enzymes. Complementary work has created many bio-hybrid Friedel-Crafts catalysts consisting of chemical catalysts anchored into biomolecular scaffolds, which display many of the same desirable characteristics. In this Review, we summarise these efforts, focussing on both mechanistic aspects and synthetic considerations, concluding with an overview of the frontiers of this field and routes towards more efficient and benign Friedel-Crafts reactions for the future of humankind.

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“…Niu et al highlight the source and function of DAOCS, enhancement of the conversion rate of penicillins to DAOC via DAOCS modification, their crystallography features and the active site prediction, as well as application perspective [ 14 ]. Prenyltransferase (PTase) are indispensable in prenylated compounds biosynthesis via transferring isoprene unit(s), Chen and Abe give some examples of microbial soluble aromatic PTases for prenylation modifications to create new unnatural prenylated compounds [ 15 ]. Similar to glycoside hydrolases or glycosyltransferases, disaccharide phosphorylases (DSPs) are modular enzymes which produce active homo-oligomers with attractive properties, especially specific disaccharides.…”

Section: Enzymes and Proteinsmentioning

confidence: 99%