Jeon, Byung-sun Huang, Teng-Yi Ruszczycky, Mark W. Choi, Sei-hyun Kim, Namho Franklin, Joseph Livy Hung, Shang-Cheng Liu, Hung-wen 2024-01-19T13:02:33Z 2024-01-19T13:02:33Z 2022-01-10 2022-01 0040-4020 https://pubs.kist.re.kr/handle/201004/115902 Biosynthesis of spinosyn A in Saccharopolyspora spinosa involves a 1,4-dehydration followed by an intramolecular [4 + 2]-cycloaddition catalyzed by SpnM and SpnF, respectively. The cycloaddition also takes place in the absence of SpnF leading to questions regarding its mechanism of catalysis and biosynthetic role. Substrate analogs were prepared with an unactivated dienophile or an acyclic structure and found to be unreactive consistent with the importance of these features for cyclization. The SpnM-catalyzed dehydration reaction was also found to yield a byproduct corresponding to the C11 = C12 cis isomer of the SpnF substrate. This byproduct is stable both in the presence and absence of SpnF; how-ever, relative production of the SpnM product and byproduct could be shifted in favor of the former by including SpnF or the dehydrogenase SpnJ in the reaction. This result suggests a potential interplay between the enzymes of spinosyn A biosynthesis that may help to improve the efficiency of the pathway. (c) 2021 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation Article 10.1016/j.tet.2021.132569 1 Tetrahedron, v.103 Tetrahedron 103 N scie scopus 000727184000022 Chemistry, Organic Chemistry Article CATALYZED 4+2 CYCLOADDITION DIELS-ALDER REACTIONS SPNF IDENTIFICATION MECHANISM INSIGHTS Enzyme [4+2]-cycloaddition Cyclase Biosynthesis Spinosyn