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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>
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Kim, Yang-Rae,Lai, Stanley C. S.,McKelvey, Kim,Zhang, Guohui,Perry, David,Miller, Thomas S.,Unwin, Patrick R. American Chemical Society 2015 JOURNAL OF PHYSICAL CHEMISTRY C - Vol.119 No.30
<P>The mechanism and kinetics of the electrochemical nucleation and growth of palladium (Pd) nanoparticles (NPs) on carbon electrodes have been investigated using a microscale meniscus cell on both highly oriented pyrolytic graphite (HOPG) and a carbon-coated transmission electron microscopy (TEM) grid. Using a microscale meniscus cell, it is possible to monitor the initial stage of electrodeposition electrochemically, while the ability to measure directly on a TEM grid allows subsequent high-resolution microscopy characterization which provides detailed nanoscopic and kinetic information. TEM analysis clearly shows that Pd is electrodeposited in the form of NPs (approximately 1–2 nm diameter) that aggregate into extensive nanocrystal-type structures. This gives rise to a high NP density. This mechanism is shown to be consistent with double potential step chronoamperometry measurements on HOPG, where a forward step generates electrodeposited Pd and the reverse step oxidizes the surface of the electrodeposited Pd to Pd oxide. The charge passed in these transients can be used to estimate the amounts of NPs electrodeposited and their size. Good agreement is found between the electrochemically determined parameters and the microscopy measurements. A model for electrodeposition based on the nucleation of NPs that aggregate to form stable structures is proposed that is used to analyze data and extract kinetics. This simple model reveals considerable information on the NP nucleation rate, the importance of aggregation in the deposition process, and quantitative values for the aggregation rate.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2015/jpccck.2015.119.issue-30/acs.jpcc.5b03513/production/images/medium/jp-2015-03513y_0011.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp5b03513'>ACS Electronic Supporting Info</A></P>
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Qu, Xuesong,Yang, Hyun Kyoung,Pan, Guohui,Chung, Jong Won,Moon, Byung Kee,Choi, Byung Chun,Jeong, Jung Hyun American Chemical Society 2011 Inorganic Chemistry Vol.50 No.8
<P>Hexagonal monodisperse NaCeF(4) and NaCeF(4):Tb(3+) nanorods have been successfully synthesized by a polyol-mediated solvothermal route with ethylene glycol (EG) as solvent. The crystalline phase, size, morphology, and luminescence properties were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and photoluminescence (PL) spectra as well as dynamic decays. The experimental results indicate that the content of NH(4)F and NaNO(3) are crucial in controlling product morphology and size. Nanorods with different aspect ratios could be controllably obtained under settled conditions. Shape-dependent luminescence and energy transfer routes from Ce(3+) to Tb(3+) in NaCeF(4):Tb(3+) nanorods were observed by the modified local crystal field environment around rare earth ions. The 4f-5d transitions of Ce(3+) ions have much higher sensitivity to the anisotropic shape of samples than that of Tb(3+) ions.</P>
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Near-Infrared Laser Stimulation of the Auditory Nerve in Guinea Pigs
Tian Guan,Jian Wang,Muqun Yang,Kai Zhu,Yong Wang,Guohui Nie 한국광학회 2016 Current Optics and Photonics Vol.20 No.2
This study has investigated the feasibility of 980-nm low-energy pulsed near-infrared laser stimulationto evoke auditory responses, as well as the effects of radiant exposure and pulse duration on auditoryresponses. In the experiments, a hole was drilled in the basal turn of the cochlea in guinea pigs. An opticalfiber with a 980-nm pulsed infrared laser was inserted into the hole, orientating the spiral ganglion cellsin the cochlea. To model deafness, the tympanic membrane was mechanically damaged. Acousticallyevoked compound action potentials (ACAPs) were recorded before and after deafness, and optically evokedcompound action potentials (OCAPs) were recorded after deafness. Similar spatial selectivity between opticaland acoustical stimulation was found. In addition, OCAP amplitudes increased with radiant exposure,indicating a photothermal mechanism induced by optical stimulation. Furthermore, at a fixed radiantexposure, OCAP amplitudes decreased as pulse duration increased, suggesting that optical stimulation mightbe governed by the time duration over which the energy is delivered. Thus, the current experiments havedemonstrated that a 980-nm pulsed near-infrared laser with low energy can evoke auditory neural responsessimilar to those evoked by acoustical stimulation. This approach could be used to develop optical cochlearimplants.
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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
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Feng, Chao,Song, Ruixi,Sun, Guohui,Kong, Ming,Bao, Zixian,Li, Yang,Cheng, Xiaojie,Cha, Dongsu,Park, Hyunjin,Chen, Xiguang American Chemical Society 2014 Biomacromolecules Vol.15 No.3
<P>We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for <I>P</I><SUB>app</SUB> values of DOX, which was 1.07–1.15 folds and 1.28–1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2014/bomaf6.2014.15.issue-3/bm401890x/production/images/medium/bm-2013-01890x_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm401890x'>ACS Electronic Supporting Info</A></P>
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Redox-Dependent Spatially Resolved Electrochemistry at Graphene and Graphite Step Edges
Gü,ell, Aleix G.,Cuharuc, Anatolii S.,Kim, Yang-Rae,Zhang, Guohui,Tan, Sze-yin,Ebejer, Neil,Unwin, Patrick R. American Chemical Society 2015 ACS NANO Vol.9 No.4
<P>The electrochemical (EC) behavior of mechanically exfoliated graphene and highly oriented pyrolytic graphite (HOPG) is studied at high spatial resolution in aqueous solutions using Ru(NH<SUB>3</SUB>)<SUB>6</SUB><SUP>3+/2+</SUP> as a redox probe whose standard potential sits close to the intrinsic Fermi level of graphene and graphite. When scanning electrochemical cell microscopy (SECCM) data are coupled with that from complementary techniques (AFM, micro-Raman) applied to the same sample area, different time-dependent EC activity between the basal planes and step edges is revealed. In contrast, other redox couples (ferrocene derivatives) whose potential is further removed from the intrinsic Fermi level of graphene and graphite show uniform and high activity (close to diffusion-control). Macroscopic voltammetric measurements in different environments reveal that the time-dependent behavior after HOPG cleavage, peculiar to Ru(NH<SUB>3</SUB>)<SUB>6</SUB><SUP>3+/2+</SUP>, is not associated particularly with any surface contaminants but is reasonably attributed to the spontaneous delamination of the HOPG with time to create partially coupled graphene layers, further supported by conductive AFM measurements. This process has a major impact on the density of states of graphene and graphite edges, particularly at the intrinsic Fermi level to which Ru(NH<SUB>3</SUB>)<SUB>6</SUB><SUP>3+/2+</SUP> is most sensitive. Through the use of an improved voltammetric mode of SECCM, we produce movies of potential-resolved and spatially resolved HOPG activity, revealing how enhanced activity at step edges is a subtle effect for Ru(NH<SUB>3</SUB>)<SUB>6</SUB><SUP>3+/2+</SUP>. These latter studies allow us to propose a microscopic model to interpret the EC response of graphene (basal plane and edges) and aged HOPG considering the nontrivial electronic band structure.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-4/acsnano.5b00550/production/images/medium/nn-2015-00550c_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5b00550'>ACS Electronic Supporting Info</A></P>
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