Towards universal synthetic heterotrophy using a metabolic coordinator

Sullivan, Sean F.; Shetty, Anuj; Bharadwaj, Tharun; Krishna, Naveen B.; Trivedi, Vikas D.; Gopinarayanan, Venkatesh Endalur; Chappell, Todd C.; Sellers, Daniel; Kumar, Raj; Nair, Nikhil U.

doi:10.1016/j.ymben.2023.07.001

Cited by 2 publications

(1 citation statement)

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“…(Bradley et al, 2016;Budisa et al, 2020)]. The latter is an excellent example of the process of assimilation of non-native substrates, also referred to in the literature as synthetic heterotrophy (Sullivan et al, 2023), which is relevant not only to the design of synthetic life but also to cell regulation, as it is a technology that diverts synthetic metabolism to optimize biomass formation.…”

Section: Introductionmentioning

confidence: 99%

Synthetic biology encompasses metagenomics, ecosystems, and biodiversity sustainability within its scope

Levin,

Budisa

2023

Front. Synth. Biol.

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We envision the convergence of synthetic biology (SynBio) and metagenomics as a significant development for the engineering of complex biological systems. The entire biosphere with its diverse life forms can also be considered as a reservoir for evolutionary innovations and a source of modules for SynBio. Metagenomics, which is a large part of biodiversity, should be considered as an important source of modules. The abstraction hierarchy of amalgamating SynBio and metagenomics (“synthetic metagenomics”) entails the standardized integration of parts, devices, circuits, and modules into functional chassis. These principles transcend the boundaries of single cell design and apply to the engineering of biodiversity sustainability in multicellular entities, their interconnections, and their dynamics in communities and whole ecosystems. Examples include applications in environmental sustainability, such as analysis of antimicrobial resistance in waste management, bioremediation of oil spills, and degradation of plastics. Future research and experimental interventions will ultimately provide a strong link between bioengineering, metagenomics, microbial consortia, ecosystems, and biodiversity sustainability under the umbrella of synthetic biology.

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Section: Introductionmentioning

confidence: 99%

Synthetic biology encompasses metagenomics, ecosystems, and biodiversity sustainability within its scope

Levin,

Budisa

2023

Front. Synth. Biol.

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Computational studies on the catalytic potential of the double active site for enzyme engineering

Krishna,

Roopa,

Pravin Kumar

et al. 2024

Sci Rep

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Proteins possessing double active sites have the potential to revolutionise enzyme design strategies. This study extensively explored an enzyme that contains both a natural active site (NAS) and an engineered active site (EAS), focusing on understanding its structural and functional properties. Metadynamics simulations were employed to investigate how substrates interacted with their respective active sites. The results revealed that both the NAS and EAS exhibited similar minimum energy states, indicating comparable binding affinities. However, it became apparent that the EAS had a weaker binding site for the substrate due to its smaller pocket and constrained conformation. Interestingly, the EAS also displayed dynamic behaviour, with the substrate observed to move outside the pocket, suggesting the possibility of substrate translocation. To gain further insights, steered molecular dynamics (SMD) simulations were conducted to study the conformational changes of the substrate and its interactions with catalytic residues. Notably, the substrate adopted distinct conformations, including near-attack conformations, in both the EAS and NAS. Nevertheless, the NAS demonstrated superior binding minima for the substrate compared to the EAS, reinforcing the observation that the engineered active site was less favourable for substrate binding due to its limitations. The QM/MM (Quantum mechanics and molecular mechanics) analyses highlight the energy disparity between NAS and EAS. Specifically, EAS exhibited elevated energy levels due to its engineered active site being located on the surface. This positioning exposes the substrate to solvents and water molecules, adding to the energy challenge. Consequently, the engineered enzyme did not provide a significant advantage in substrate binding over the single active site protein. Further, the investigation of internal channels and tunnels within the protein shed light on the pathways facilitating transport between the two active sites. By unravelling the complex dynamics and functional characteristics of this double-active site protein, this study offers valuable insights into novel strategies of enzyme engineering. These findings establish a solid foundation for future research endeavours aimed at harnessing the potential of double-active site proteins in diverse biotechnological applications.

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Towards universal synthetic heterotrophy using a metabolic coordinator

Cited by 2 publications

References 76 publications

Synthetic biology encompasses metagenomics, ecosystems, and biodiversity sustainability within its scope

Synthetic biology encompasses metagenomics, ecosystems, and biodiversity sustainability within its scope

Computational studies on the catalytic potential of the double active site for enzyme engineering

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