Metabolic disassembler for understanding and predicting the biosynthetic units of natural products.

BACKGROUND: Natural products are the source of various functional materials such as medicines, and understanding their biosynthetic pathways can provide information that is helpful for their effective production through the synthetic biology approach. A number of studies have aimed to predict biosynthetic pathways from their chemical structures in a retrosynthesis manner; however, sometimes the calculation finishes without reaching the starting material from the target molecule. In order to address this problem, the method to find suitable starting materials is required. RESULTS: In this study, we developed a predictive workflow named the Metabolic Disassembler that automatically disassembles the target molecule structure into relevant biosynthetic units (BUs), which are the substructures that correspond to the starting materials in the biosynthesis pathway. This workflow uses a biosynthetic unit library (BUL), which contains starting materials, key intermediates, and their derivatives. We obtained the starting materials from the KEGG PATHWAY database, and 765 BUs were registered in the BUL. We then examined the proposed workflow to optimize the combination of the BUs. To evaluate the performance of the proposed Metabolic Disassembler workflow, we used 943 molecules that are included in the secondary metabolism maps of KEGG PATHWAY. About 95.8% of them (903 molecules) were correctly disassembled by our proposed workflow. For comparison, we also implemented a genetic algorithm-based workflow, and found that the accuracy was only about 52.0%. In addition, for 90.7% of molecules, our workflow finished the calculation within one minute. CONCLUSIONS: The Metabolic Disassembler enabled the effective disassembly of natural products in terms of both correctness and computational time. It also outputs automatically highlighted color-coded substructures corresponding to the BUs to help users understand the calculation results. The users do not have to specify starting molecules in advance, and can input any target molecule, even if it is not in databases. Our workflow will be very useful for understanding and predicting the biosynthesis of natural products.

Two Japanese Pediatric Patients With Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in the CCNO gene.

Primary ciliary dyskinesia (PCD) is a rare congenital disorder caused by pathogenic variants of genes related to cilia. Here, we report two Japanese pediatric patients with PCD caused by pathogenic compound heterozygous variants in the cyclin O (CCNO) gene (Case 1, NM_021147.4:c.[262C>T];[781delC], p.[Gln88Ter];[Leu261fs]; Case 2, c.[262C>T];[c.248_252dupTGCCC], p.[Gln88Ter];[Gly85fs]). The clinical symptoms of the patients were varied. Neither of the patients had situs inversus. Transmission electron microscopy of the respiratory cilia from the nasal mucosa in Case 1 showed a remarkable reduction of cilia and the few residual cilia had central pair defects and microtubular disorganization.

Two Pediatric Cases of Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in Oral-Facial-Digital Syndrome Gene, OFD1.

Primary ciliary dyskinesia (PCD) is a hereditary disease caused by genes related to motile cilia. We report two male pediatric cases of PCD caused by hemizygous pathogenic variants in the OFD1 centriole and centriolar satellite protein (OFD1) gene. The variants were NM_003611.3: c.[2789_2793delTAAAA] (p.[Ile930LysfsTer8]) in Case 1 and c.[2632_2635delGAAG] (p.[Glu878LysfsTer9]) in Case 2. Both cases had characteristic recurrent respiratory infections. Neither case had symptoms of oral-facial-digital syndrome type I. We identified a variant (c.2632_2635delGAAG) that has not been previously reported in any case of OFD1-PCD.

Anisotropic diamond etching through thermochemical reaction between Ni and diamond in high-temperature water vapour.

Diamond possesses excellent physical and electronic properties, and thus various applications that use diamond are under development. Additionally, the control of diamond geometry by etching technique is essential for such applications. However, conventional wet processes used for etching other materials are ineffective for diamond. Moreover, plasma processes currently employed for diamond etching are not selective, and plasma-induced damage to diamond deteriorates the device-performances. Here, we report a non-plasma etching process for single crystal diamond using thermochemical reaction between Ni and diamond in high-temperature water vapour. Diamond under Ni films was selectively etched, with no etching at other locations. A diamond-etching rate of approximately 8.7 µm/min (1000 °C) was successfully achieved. To the best of our knowledge, this rate is considerably greater than those reported so far for other diamond-etching processes, including plasma processes. The anisotropy observed for this diamond etching was considerably similar to that observed for Si etching using KOH.

Inversion channel diamond metal-oxide-semiconductor field-effect transistor with normally off characteristics.

We fabricated inversion channel diamond metal-oxide-semiconductor field-effect transistors (MOSFETs) with normally off characteristics. At present, Si MOSFETs and insulated gate bipolar transistors (IGBTs) with inversion channels are widely used because of their high controllability of electric power and high tolerance. Although a diamond semiconductor is considered to be a material with a strong potential for application in next-generation power devices, diamond MOSFETs with an inversion channel have not yet been reported. We precisely controlled the MOS interface for diamond by wet annealing and fabricated p-channel and planar-type MOSFETs with phosphorus-doped n-type body on diamond (111) substrate. The gate oxide of Al2O3 was deposited onto the n-type diamond body by atomic layer deposition at 300 °C. The drain current was controlled by the negative gate voltage, indicating that an inversion channel with a p-type character was formed at a high-quality n-type diamond body/Al2O3 interface. The maximum drain current density and the field-effect mobility of a diamond MOSFET with a gate electrode length of 5 µm were 1.6 mA/mm and 8.0 cm(2)/Vs, respectively, at room temperature.