A combined experimental and modelling approach for the Weimberg pathway optimisation

• DOI: 10.1038/s41467-020-14830-y
• Publication Date: 2020-02-27T11:04:32Z
• Authors: Lu Shen; Martha Kohlhaas; Junichi Enoki; Roland Meier; Bernhard Schönenb...; Roland Wohlgemuth; Robert Kourist; Felix Niemeyer; David van Niekerk; Christopher Bräsen; Jochen Niemeyer; Jacky Snoep; Bettina Siebers
• Keywords: 0303 health sciences; Xylose; Science; Q; Chemie; 7. Clean energy; Article; 12. Responsible consumption; 03 medical and health sciences; Bioreactors; Bacterial Proteins; Metabolic Engineering; Models, Chemical; Biofuels; Caulobacter crescentus; Carbohydrate Metabolism; Ketoglutaric Acids; Computer Simulation; SDG 7 - Affordable and Clean Energy; Oxidoreductases; Oxidation-Reduction; Hydro-Lyases; Metabolic Networks and Pathways; NADP

The oxidative Weimberg pathway for the five-step pentose degradation to α-ketoglutarate is a key route sustainable bioconversion of lignocellulosic biomass added-value products and biofuels. from Caulobacter crescentus has been employed in in-vivo metabolic engineering with intact cells in-vitro enzyme cascades. performance such approaches often hampered by systems complexity, caused non-linear kinetics allosteric regulatory mechanisms. Here we report an iterative approach construct validate quantitative model pathway. Two sensitive points have identified as follows: (1) product inhibition dehydrogenases (particularly absence efficient NAD+ recycling mechanism) (2) balancing activities dehydratases. resulting utilized design cascades optimized conversion analyse C. cresensus cell-free extracts.