6247-62-7Relevant academic research and scientific papers
Elucidation of the Herbicidin Tailoring Pathway Offers Insights into Its Structural Diversity
Pan, Hai-Xue,Chen, Zhang,Zeng, Tianfang,Jin, Wen-Bing,Geng, Yujie,Lin, Geng-Min,Zhao, Juan,Li, Wei-Tao,Xiong, Zijun,Huang, Sheng-Xiong,Zhai, Xin,Liu, Hung-Wen,Tang, Gong-Li
supporting information, p. 1374 - 1378 (2019/02/26)
The biosynthetic gene clusters for herbicidins (hbc) and aureonuclemycin (anm) were identified in Streptomyces sp. KIB-027 and Streptomyces aureus, respectively. The roles of genes possibly involved in post-core-assembly steps in herbicidin biosynthesis i
Discovery and Engineering of Pathways for Production of α-Branched Organic Acids
Blaisse, Michael R.,Dong, Hongjun,Fu, Beverly,Chang, Michelle C. Y.
supporting information, p. 14526 - 14532 (2017/10/24)
Cell-based synthesis offers many opportunities for preparing small molecules from simple renewable carbon sources by telescoping multiple reactions into a single fermentation step. One challenge in this area is the development of enzymatic carbon-carbon bond forming cycles that enable a modular disconnection of a target structure into cellular building blocks. In this regard, synthetic pathways based on thiolase enzymes to catalyze the initial carbon-carbon bond forming step between acyl coenzyme A (CoA) substrates offer a versatile route for biological synthesis, but the substrate diversity of such pathways is currently limited. In this report, we describe the identification and biochemical characterization of a thiolase-ketoreductase pair involved in production of branched acids in the roundworm, Ascaris suum, that demonstrates selectivity for forming products with an α-methyl branch using a propionyl-CoA extender unit. Engineering synthetic pathways for production of α-methyl acids in Escherichia coli using these enzymes allows the construction of microbial strains that produce either chiral 2-methyl-3-hydroxy acids (1.1 ± 0.2 g L-1) or branched enoic acids (1.12 ± 0.06 g L-1) in the presence of a dehydratase at 44% and 87% yield of fed propionate, respectively. In vitro characterization along with in vivo analysis indicates that the ketoreductase is the key driver for selectivity, forming predominantly α-branched products even when paired with a thiolase that highly prefers unbranched linear products. Our results expand the utility of thiolase-based pathways and provide biosynthetic access to α-branched compounds as precursors for polymers and other chemicals.
