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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>
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>
( Yanyan Liu ),( Hojin Ryu ),( Beibei Ge ),( Guohui Pan ),( Lei Sun ),( Kyungseok Park ),( Kecheng Zhang ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.12
Wuyiencin is produced by Streptomyces ahygroscopicus var. wuyiensis CK-15 and is widely used as an antifungal agent in agriculture. Analysis of wuyiencin biosynthetic gene clusters reveals wysR, a member of the LAL-family of transcriptional regulatory genes. WysR consists of an Nterminal PAS domain and a LuxR family C-terminal helix-turn-helix motif. However, the roles of wysR in wuyiencin biosynthesis are largely unknown. In this study, we showed that inactivation of wysR resulted in the complete loss of wuyiencin production, which could be restored by complementation with a single copy of wysR. Furthermore, we successfully increased wuyiencin production to a significantly higher level by overexpression of wysR in S. wuyiensis CK-15. Quantitative real-time RT-PCR analysis showed that WysR regulates wuyiencin biosynthesis by modulating other putative regulatory genes. Thus, WysR was identified as an activator of wuyiencin biosynthesis, and overexpression of wysR gene proved to be an effective strategy for improving wuyiencin production.