Cofactor NAD(P)H Regeneration Inspired by Heterogeneous Pathways

Wang, Xiaodong; Saba, Tony; Yiu, Humphrey H. P.; Howe, Russell F.; Anderson, James A.; Shi, Jiafu

doi:10.1016/j.chempr.2017.04.009

Cited by 353 publications

(382 citation statements)

References 89 publications

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“…In such a way, this approach overcomes the use of this expensive α‐keto acid as a starting material . Furthermore, compared to other cascades that use amino acid dehydrogenases, there is no requirement for an expensive cofactor such as NADH when aminotransferases are used …”

Section: Methodssupporting

confidence: 92%

Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L‐ and D‐Homoalanine

et al. 2018

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Unnatural amino acids attract growing attention for pharmaceutical applications as they are useful building blocks for the synthesis of a number of chiral drugs. Here, we describe a two‐step enzymatic method for the asymmetric synthesis of homoalanine from L‐methionine, a cheap and readily available natural amino acid. First, the enzyme L‐methionine γ‐lyase (METase), from Fusobacterium nucleatum, catalyzed the γ‐elimination of L‐methionine to 2‐oxobutyrate. Second, an amino acid aminotransferase catalyzed the asymmetric conversion of 2‐oxobutyrate to either L‐ or D‐homoalanine. The L‐branched chain amino acid aminotransferase from Escherichia coli (eBCAT), using L‐glutamate as amino donor, produced L‐homoalanine (32.5 % conv., 28 % y, 99 % ee) and the D‐amino acid aminotransferase from Bacillus sp. (DATA) used D‐alanine as amino donor to produce D‐homoalanine (87.5 % conv., 69 % y, 90 % ee). Thus, this concept allows for the first time the synthesis of both enantiomers of this important unnatural amino acid.

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Section: Methodssupporting

confidence: 92%

Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L‐ and D‐Homoalanine

et al. 2018

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“…The primary source of NADPH in yeasts is the pentose phosphate pathway (PPP), which oxidizes a hexose sugar with concomitant loss of two equivalents of CO 2 , decreasing theoretical carbon yields (22). Therefore, decoupling NADPH generation from central carbon metabolism may help maximize carbon flux for the production of desired metabolites (20). …”

mentioning

confidence: 99%

Light-driven fine chemical production in yeast biohybrids

Guo

Suástegui

Sakimoto

et al. 2018

Science

321

256

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Inorganic-biological hybrid systems have potential to be sustainable, efficient, and versatile chemical synthesis platforms by integrating the light-harvesting properties of semiconductors with the synthetic potential of biological cells. We have developed a modular bioinorganic hybrid platform that consists of highly efficient light-harvesting indium phosphide nanoparticles and genetically engineered Saccharomyces cerevisiae: a workhorse microorganism in biomanufacturing. The yeast harvests photo-generated electrons from the illuminated nanoparticles and uses them for the cytosolic regeneration of redox cofactors. This enables the decoupling of biosynthesis and cofactor regeneration, facilitating a carbon- and energy-efficient production of the metabolite shikimic acid – a common precursor for several drugs and fine chemicals. Our work provides a platform for the rational design of biohybrids for efficient biomanufacturing processes with higher complexity and functionality.

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“…[24] Recycling strategies are extensive [24][25][26][27][28] but only one of these (homogeneous enzymatic regeneration) has been adopted for practical use. [24,29] Although well-established, the approach is far from optimal as the bulk solution chemistry is slow and inefficient, particularly with low cofactor concentrations, and the presence of any further soluble chemicals increases complexity in product separation downstream. With its combination of nanoconfinement, cofactor regeneration and ability to drive the overall reaction, the electrochemical leaf carries out organic synthesis with in-built, localised cofactor recycling, and is exceptionally easy; once scaled up or integrated with automation, it could revolutionise biocatalysis.…”

Section: Giorgio Morello Holds a Master's Degree (2015)mentioning

confidence: 99%

“…Oxidoreductases are one of the largest enzyme classes and are vital to the pharmaceutical industry; their requirement for nicotinamide cofactors as a hydride source/sink makes them perfect candidates for use in the electrochemical leaf technology. Given their expense and requirement in stoichiometric amounts, industry must recycle nicotinamide cofactors in situ to allow reactions to progress . Recycling strategies are extensive but only one of these (homogeneous enzymatic regeneration) has been adopted for practical use .…”

Section: Introductionmentioning

confidence: 99%

Electrified Nanoconfined Biocatalysis with Rapid Cofactor Recycling

et al. 2019

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In living cells, the overall rates of catalytic reaction chains (cascades) are massively enhanced by nanoconfinement of enzymes in tiny enclosed volumes: presented in such a way, interdependent catalysts are highly concentrated, and distances (active site‐to‐active site) across which intermediates and cofactors must diffuse, may be tiny. In a parallel technology exploiting this principle, enzyme cascades are powered, amplified, and monitored in real time as they work in concert, being nanoconfined within the pores of an electrically conductive metal oxide electrode. The technology, nicknamed the electrochemical leaf, mimics chloroplast biosynthesis by exploiting nicotinamide adenine dinucleotide (NADP(H)) recycling catalysed by the flavoenzyme, ferredoxin NADP+ reductase (FNR). Adsorbed on the inner walls of the nanopores, FNR rapidly transfers electrons between the electrode and NADP(H). This activity is coupled to an oxidoreductase enzyme, also nanoconfined within the pores, which recycles the cofactor and selectively synthesises a desired product or senses an analyte. Use of catalyst and cofactor is very efficient. The technology is simple, inexpensive and adaptable, and scalable to both microscopic levels (diagnostics) and macroscopic levels (organic synthesis). Whereas native FNR is specific for NADP(H), the technology can be extended by genetic engineering to include NAD(H) as recycling cofactor.

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Cofactor NAD(P)H Regeneration Inspired by Heterogeneous Pathways

Cited by 353 publications

References 89 publications

Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L‐ and D‐Homoalanine

Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L‐ and D‐Homoalanine

Light-driven fine chemical production in yeast biohybrids

Electrified Nanoconfined Biocatalysis with Rapid Cofactor Recycling

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