6oz1

Crystal structure of the adenylation (A) domain of the carboxylate reductase (CAR) GR01_22995 from Mycobacterium chelonae

spinqualitylabelsall models 6oz1, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6oz1 is a 1 chain structure with sequence from Mycobacteroides chelonae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.97Å Ligands: AMP, CL, GOL, SIN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0E3TT64_MYCCH Catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes.[HAMAP-Rule:MF_02247] Publication Abstract from PubMed Production of platform chemicals from renewable feedstocks is becoming increasingly important due to concerns on environmental contamination, climate change, and depletion of fossil fuels. Adipic acid (AA), 6-aminocaproic acid (6-ACA) and 1,6-hexamethylenediamine (HMD) are key precursors for nylon synthesis, which are currently produced primarily from petroleum-based feedstocks. In recent years, the biosynthesis of adipic acid from renewable feedstocks has been demonstrated using both bacterial and yeast cells. Here we report the biocatalytic conversion/transformation of AA to 6-ACA and HMD by carboxylic acid reductases (CARs) and transaminases (TAs), which involves two rounds (cascades) of reduction/amination reactions (AA --> 6-ACA --> HMD). Using purified wild type CARs and TAs supplemented with cofactor regenerating systems for ATP, NADPH, and amine donor, we established a one-pot enzyme cascade catalyzing up to 95% conversion of AA to 6-ACA. To increase the cascade activity for the transformation of 6-ACA to HMD, we determined the crystal structure of the CAR substrate-binding domain in complex with AMP and succinate and engineered three mutant CARs with enhanced activity against 6-ACA. In combination with TAs, the CAR L342E protein showed 50-75% conversion of 6-ACA to HMD. For the transformation of AA to HMD (via 6-ACA), the wild type CAR was combined with the L342E variant and two different TAs resulting in up to 30% conversion to HMD and 70% to 6-ACA. Our results highlight the suitability of CARs and TAs for several rounds of reduction/amination reactions in one-pot cascade systems and their potential for the biobased synthesis of terminal amines. One-Pot Biocatalytic Transformation of Adipic Acid to 6-Aminocaproic Acid and 1,6-Hexamethylenediamine Using Carboxylic Acid Reductases and Transaminases.,Fedorchuk TP, Khusnutdinova AN, Evdokimova E, Flick R, Di Leo R, Stogios P, Savchenko A, Yakunin AF J Am Chem Soc. 2020 Jan 15;142(2):1038-1048. doi: 10.1021/jacs.9b11761. Epub 2020, Jan 7. PMID:31886667 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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