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Biosynthesis of thiocarboxylic acid-containing natural products

Dong, Liao-Bin ; Rudolf, Jeffrey D ; Kang, Dingding ; Wang, Nan ; He, Cyndi Qixin ; Deng, Youchao ; Huang, Yong ; Houk, K N ; Duan, Yanwen ; Shen, Ben

Nature communications, 2018-06, Vol.9 (1), p.2362-10, Article 2362 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Biosynthesis of thiocarboxylic acid-containing natural products
Autor: Dong, Liao-Bin ; Rudolf, Jeffrey D ; Kang, Dingding ; Wang, Nan ; He, Cyndi Qixin ; Deng, Youchao ; Huang, Yong ; Houk, K N ; Duan, Yanwen ; Shen, Ben
Assuntos: Acids ; Adamantane - metabolism ; Aminobenzoates - metabolism ; Aminophenols - metabolism ; Anilides - metabolism ; Biological Products - chemistry ; Biosynthesis ; Cassettes ; Coenzyme A ; Congeners ; Density functional theory ; Escherichia coli ; Genomes ; Multigene Family ; Natural products ; Pharmacology ; Polycyclic Compounds - metabolism ; Proteins ; Solvation ; Streptomyces - genetics ; Streptomyces - metabolism ; Sulfur ; Sulfur - metabolism
É parte de: Nature communications, 2018-06, Vol.9 (1), p.2362-10, Article 2362
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Thiocarboxylic acid-containing natural products are rare and their biosynthesis and biological significance remain unknown. Thioplatensimycin (thioPTM) and thioplatencin (thioPTN), thiocarboxylic acid congeners of the antibacterial natural products platensimycin (PTM) and platencin (PTN), were recently discovered. Here we report the biosynthetic origin of the thiocarboxylic acid moiety in thioPTM and thioPTN. We identify a thioacid cassette encoding two proteins, PtmA3 and PtmU4, responsible for carboxylate activation by coenzyme A and sulfur transfer, respectively. ThioPTM and thioPTN bind tightly to β-ketoacyl-ACP synthase II (FabF) and retain strong antibacterial activities. Density functional theory calculations of binding and solvation free energies suggest thioPTM and thioPTN bind to FabF more favorably than PTM and PTN. Additionally, thioacid cassettes are prevalent in the genomes of bacteria, implicating that thiocarboxylic acid-containing natural products are underappreciated. These results suggest that thiocarboxylic acid, as an alternative pharmacophore, and thiocarboxylic acid-containing natural products may be considered for future drug discovery.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Biosynthesis of thiocarboxylic acid-containing natural products

Dong, Liao-Bin ; Rudolf, Jeffrey D ; Kang, Dingding ; Wang, Nan ; He, Cyndi Qixin ; Deng, Youchao ; Huang, Yong ; Houk, K N ; Duan, Yanwen ; Shen, Ben

England: Nature Publishing Group

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