Structural synthetic biology strategy for the design of a new metabolic pathway

To date, notable successes have been made in producing valuable chemicals and fuels from renewable resources by simply modifying and optimizing the metabolic pathways in microorganisms. However, to design a more efficient and desirable pathway with high efficiency from ubiquitously existing multi-branched and multi-level regulated ones, a new approach is needed other than conventional systematic analysis of every bottlenecks embedded in the biosynthetic pathways. Here, we present a strategy combining rational enzyme design and synthetic biology to construct a new metabolic pathway which evades from the highly regulated nature. As a proof-of-concept, we implemented our approach to the design of a new L-methionine biosynthetic pathway. To this end, structure of the MetZ enzyme, which is a key to the construction of new biosynthetic pathway in Corynebacterium glutamicum, was modelled, and its substrate specificity was rationally altered toward a substrate required for redirecting the metabolic flux in the pathway. Furthermore, we used mutational approach to relieve feedback inhibition of other enzymes which regulate the metabolic flux in the methionine biosynthetic pathway. As a result, the L-methionine level reached a gram scale in flask culture by recombinant Corynebacterium glutamicum with the methionine biosynthetic pathway. We demonstrate that the “structural synthetic biology” strategy can boost our ability to generate a more efficient metabolic pathway for the production of valuable chemicals

Formation of Warped Disks by Galactic Fly-by Encounters. I. Stellar Disks

Warped disks are almost ubiquitous among spiral galaxies. Here we revisit and test the `fly-by scenario' of warp formation, in which impulsive encounters between galaxies are responsible for warped disks. Based on N-body simulations, we investigate the morphological and kinematical evolution of the stellar component of disks when galaxies undergo fly-by interactions with adjacent dark matter halos. We find that the so-called `S'-shaped warps can be excited by fly-bys and sustained for even up to a few billion years, and that this scenario provides a cohesive explanation for several key observations. We show that disk warp properties are governed primarily by the following three parameters; (1) the impact parameter, i.e., the minimum distance between two halos, (2) the mass ratio between two halos, and (3) the incident angle of the fly-by perturber. The warp angle is tied up with all three parameters, yet the warp lifetime is particularly sensitive to the incident angle of the perturber. Interestingly, the modeled S-shaped warps are often non-symmetric depending on the incident angle. We speculate that the puzzling U- and L-shaped warps are geometrically superimposed S-types produced by successive fly-bys with different incident angles, including multiple interactions with a satellite on a highly elongated orbit.Comment: 16 pages, 13 figures, 3 tables. Accepted for publication in Ap