Homocitrate synthase (HCS) catalyzes aldol-type condensation of acetyl coenzyme A (acetyl-CoA) and ␣-ketoglutarate (␣-KG) to synthesize homocitrate (HC), which is the first and committed step in the lysine biosynthetic pathway through ␣-aminoadipate. As known in most enzymes catalyzing the first reactions in amino acid biosynthetic pathways, HCS is regulated via feedback inhibition by the end product, lysine. Here, we determined the crystal structures of HCS from Thermus thermophilus complexed with ␣-KG, HC, or lysine. In the HC complex, the C1-carboxyl group of HC, which is derived from acetylCoA, is hydrogen-bonded with His-292* from another subunit (indicated by the asterisk), indicating direct involvement of this residue in the catalytic mechanism of HCS. The crystal structure of HCS complexed with lysine showed that lysine is bound to the active site with rearrangement of amino acid residues in the substrate-binding site, which accounts for the competitive inhibition by lysine with ␣-KG. Comparison between the structures suggests that His-72, which is conserved in lysine-sensitive HCSs and binds the C5-carboxyl group of ␣-KG, serves as a switch for the conformational change. Replacement of His-72 by leucine made HCS resistant to lysine inhibition, demonstrating the regulatory role of this conserved residue.
In Thermus thermophilus homocitrate synthase (HCS) catalyzes the initial reaction of lysine biosynthesis through K K-aminoadipic acid, synthesis of homocitrate from 2-oxoglutarate and acetyl-CoA. HCS is strongly inhibited by lysine, indicating that the biosynthesis is regulated by the endproduct at the initial reaction in the pathway. HCS also catalyzes the reaction using oxaloacetate in place of 2-oxoglutarate as a substrate, similar to citrate synthase in the tricarboxylic acid cycle. Several other properties of Thermus HCS and an evolutionary relationship of the biosynthetic pathway in the bacterium to other metabolic pathways are also described. ß
Asian countries have abundant resources of natural fibers, but unfortunately, they have not been optimally utilized. The facts showed that from 2014 to 2020, there was a shortfall in meeting national demand of over USD 2.75 million per year. Therefore, in order to develop the utilization and improve the economic potential as well as the sustainability of natural fibers, a comprehensive review is required. The study aimed to demonstrate the availability, technological processing, and socio-economical aspects of natural fibers. Although many studies have been conducted on this material, it is necessary to revisit their potential from those perspectives to maximize their use. The renewability and biodegradability of natural fiber are part of the fascinating properties that lead to their prospective use in automotive, aerospace industries, structural and building constructions, bio packaging, textiles, biomedical applications, and military vehicles. To increase the range of applications, relevant technologies in conjunction with social approaches are very important. Hence, in the future, the utilization can be expanded in many fields by considering the basic characteristics and appropriate technologies of the natural fibers. Selecting the most prospective natural fiber for creating national products can be assisted by providing an integrated management system from a digitalized information on potential and related technological approaches. To make it happens, collaborations between stakeholders from the national R&D agency, the government as policy maker, and academic institutions to develop national bioproducts based on domestic innovation in order to move the circular economy forward are essential.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.