Title

Protein and process engineering towards biocatalysts useful in industrial processes

Conference Dates

September 15-19, 2019

Abstract

While progress is slower than anticipated, biocatalysts do enter an increasing number of proces-ses not just to pharmaceuticals but also to specialty and even bulk chemicals. The presentation will start with an update on some well-known and some less widely disseminated applications.

Next, we will cover two case studies from our own work, penicillin G acylase (Pen G acylase, PGA) and NADH oxidase (nox2). Both enzymes did and continue to benefit from protein engineering for optimum use in large-scale processes. Pen G acylase catalyzes amide bond formation to beta-lactam antibiotics, such as commercially important amoxicillin and cephalexin, but requires long time-on-stream as reaction yields are moderate and thus cost of goods are high. Development of continuous processes demands accurate process models [1-2], which in turn necessitates detailed knowledge about effects of immobilization and deactivation.[3]

NADH oxidase (nox2) finds use in biooxidation processes for the regeneration of NADH to NAD+.[4] However, the enzyme is sensitive to gas-liquid interfaces [5] and is turnover-limited owing to overoxidation at the active site.[6-8] We will report on progress to tackle such process stability issues.

References:

[1] MA McDonald, AS Bommarius, RW Rousseau, and MA Grover, Comp. Chem. Eng. 2019, 123, 331-343

[2] MA McDonald, AS Bommarius, MA Grover, RW Rousseau, Comp. Chem. Eng. 2019, 126C, 332-341

[3] MA McDonald, L Bromig, MA Grover, RW Rousseau, AS Bommarius, Chem. Eng. Sci., 2018, 187, 79-86

[4] G Rehn, AT Pedersen, JM Woodley, J. Mol. Catal. B: Enzymatic 2016, 134, 331-339

[5] M Dias-Gomes, B Bommarius, SR Anderson, BD Feske, JM Woodley, AS Bommarius, Adv. Synth. Cat., 2019, 361, 2574-2581

[6] BR Riebel, PR Gibbs, WB Wellborn, AS Bommarius,

Adv. Synth. Cat., 2002, 344, 1156-1169

[7] BR Riebel, PR Gibbs, WB Wellborn, AS Bommarius,

Adv. Synth. Cat., 2003, 345, 707-712

[8] JT Park, JI Hirano, V Thangavel, BR Riebel, AS Bommarius, J. Mol. Catal. B Enz. 2011, 71, 159-165

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