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Discovery of the leinamycin family of natural products by mining actinobacterial genomes
Pan, Guohui,Xu, Zhengren,Guo, Zhikai,Hindra,Ma, Ming,Yang, Dong,Zhou, Hao,Gansemans, Yannick,Zhu, Xiangcheng,Huang, Yong,Zhao, Li-Xing,Jiang, Yi,Cheng, Jinhua,Van Nieuwerburgh, Filip,Suh, Joo-Won,Duan National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.52
<P>Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.</P>
Member capacity-based progressive collapse analysis of transmission towers under wind load
Yong-Quan Li,Yong Chen,Guohui Shen,Wenjuan Lou,Weijian Zhao,Hao Wang 한국풍공학회 2021 Wind and Structures, An International Journal (WAS Vol.33 No.4
The wind-induced collapse of transmission towers has raised many concerns. Progressive collapse analysis is recognized as a promising method for the assessment of the collapse-resistant capacity of the transmission tower. The finite element model of an actual transmission tower is firstly built for the analysis, in which the dynamic behavior of the member in failure is taken into account to be in accord with the actual tower collapse. The analysis considering the main design load cases is conducted in advance to determine the case under which the tower has the potential to collapse. The incremental dynamic analysis in association with the explicit time integration algorithm is employed to perform a progressive collapse analysis, where the wind loads are simulated by using the linear filtering method, and the developed failure criterion with axial force and bending moment involved is based on the stability bearing capacity of the members. It is found the tower collapse begins with the horizontal bracing member near the waist. Then, the adjacent members, including the leg members, fail sequentially, and the tower collapses eventually with a shear-type failure. The demand to capacity ratio (DCR) in terms of bearing capacity of the member is defined to quantify the structural behavior, the location of the member that has the potential to fail, and when the initial failure occurs are thereby identified. It is concluded that compared to the member capacity-based analysis, the ultimate strain-based analysis, which is most likely to be an inelastic dynamic analysis permitting a large deformation, may overestimate the bearing capacity of the structure in wind-induced collapse.
Wind tunnel investigation on wind characteristics of flat and mountainous terrain
Jia-Wu Li,Jun Wang,Shucheng Yang,Feng Wang,Guohui Zhao 한국풍공학회 2022 Wind and Structures, An International Journal (WAS Vol.35 No.4
Wind tunnel test is often adopted to assess the site-specific wind characteristics for the design of bridges as suggested by current design standards. To investigate the wind characteristics of flat and mountainous terrain, two topographic models are tested in a boundary layer wind tunnel. The wind characteristics, including the vertical and horizontal mean wind speed distributions, the turbulence intensity, and the wind power spectra, are presented. They are investigated intensively in present study with the discussions on the effect of wind direction and the effect of topography. It is indicated that for flat terrain, the wind direction has negligible effect on the wind characteristics, however, the assumption of a homogenous wind field for the mountainous terrain is not applicable. Further, the non-homogeneous wind field can be defined based on a proposed approach if the wind tunnel test or on-site measurement is performed. The calculated turbulence intensities and wind power spectra by using the measured wind speeds are also given. It is shown that for the mountainous terrain, engineers should take into account the variability of the wind characteristics for design considerations