TY  - JOUR
A1  - Scherer, Marc
A1  - Fleishman, Sarel J.
A1  - Jones, Patrik R.
A1  - Dandekar, Thomas
A1  - Bencurova, Elena
T1  - Computational Enzyme Engineering Pipelines for Optimized Production of Renewable Chemicals
JF  - Frontiers in Bioengineering and Biotechnology
N2  - To enable a sustainable supply of chemicals, novel biotechnological solutions are required that replace the reliance on fossil resources. One potential solution is to utilize tailored biosynthetic modules for the metabolic conversion of CO2 or organic waste to chemicals and fuel by microorganisms. Currently, it is challenging to commercialize biotechnological processes for renewable chemical biomanufacturing because of a lack of highly active and specific biocatalysts. As experimental methods to engineer biocatalysts are time- and cost-intensive, it is important to establish efficient and reliable computational tools that can speed up the identification or optimization of selective, highly active, and stable enzyme variants for utilization in the biotechnological industry. Here, we review and suggest combinations of effective state-of-the-art software and online tools available for computational enzyme engineering pipelines to optimize metabolic pathways for the biosynthesis of renewable chemicals. Using examples relevant for biotechnology, we explain the underlying principles of enzyme engineering and design and illuminate future directions for automated optimization of biocatalysts for the assembly of synthetic metabolic pathways.
KW  - computational
KW  - enzyme
KW  - engineering
KW  - design
KW  - biomanufacturing
KW  - biofuel
KW  - microbes
KW  - metabolism
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240598
SN  - 2296-4185
VL  - 9
ER  - 
TY  - JOUR
A1  - Osmanoglu, Özge
A1  - Khaled AlSeiari, Mariam
A1  - AlKhoori, Hasa Abduljaleel
A1  - Shams, Shabana
A1  - Bencurova, Elena
A1  - Dandekar, Thomas
A1  - Naseem, Muhammad
T1  - Topological Analysis of the Carbon-Concentrating CETCH Cycle and a Photorespiratory Bypass Reveals Boosted CO\(_2\)-Sequestration by Plants
JF  - Frontiers in Bioengineering and Biotechnology
N2  - Synthetically designed alternative photorespiratory pathways increase the biomass of tobacco and rice plants. Likewise, some in planta–tested synthetic carbon-concentrating cycles (CCCs) hold promise to increase plant biomass while diminishing atmospheric carbon dioxide burden. Taking these individual contributions into account, we hypothesize that the integration of bypasses and CCCs will further increase plant productivity. To test this in silico, we reconstructed a metabolic model by integrating photorespiration and photosynthesis with the synthetically designed alternative pathway 3 (AP3) enzymes and transporters. We calculated fluxes of the native plant system and those of AP3 combined with the inhibition of the glycolate/glycerate transporter by using the YANAsquare package. The activity values corresponding to each enzyme in photosynthesis, photorespiration, and for synthetically designed alternative pathways were estimated. Next, we modeled the effect of the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA cycle (CETCH), which is a set of natural and synthetically designed enzymes that fix CO₂ manifold more than the native Calvin–Benson–Bassham (CBB) cycle. We compared estimated fluxes across various pathways in the native model and under an introduced CETCH cycle. Moreover, we combined CETCH and AP3-w/plgg1RNAi, and calculated the fluxes. We anticipate higher carbon dioxide–harvesting potential in plants with an AP3 bypass and CETCH–AP3 combination. We discuss the in vivo implementation of these strategies for the improvement of C3 plants and in natural high carbon harvesters.
KW  - CO2-sequestration
KW  - photorespiration
KW  - elementary modes
KW  - synthetic pathways
KW  - carboxylation
KW  - metabolic modeling
KW  - CETCH cycle
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249260
SN  - 2296-4185
VL  - 9
ER  -