- Repurposing the 3-Isocyanobutanoic Acid Adenylation Enzyme SfaB for Versatile Amidation and Thioesterification
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Genome mining of microbial natural products enables chemists not only to discover the bioactive molecules with novel skeletons, but also to identify the enzymes that catalyze diverse chemical reactions. Exploring the substrate promiscuity and catalytic mechanism of those biosynthetic enzymes facilitates the development of potential biocatalysts. SfaB is an acyl adenylate-forming enzyme that adenylates a unique building block, 3-isocyanobutanoic acid, in the biosynthetic pathway of the diisonitrile natural product SF2768 produced by Streptomyces thioluteus, and this AMP-ligase was demonstrated to accept a broad range of short-chain fatty acids (SCFAs). Herein, we repurpose SfaB to catalyze amidation or thioesterification between those SCFAs and various amine or thiol nucleophiles, thereby providing an alternative enzymatic approach to prepare the corresponding amides and thioesters in vitro.
- Zhu, Mengyi,Wang, Lijuan,He, Jing
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supporting information
p. 2030 - 2035
(2020/11/30)
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- Captopril analogues as metallo-β-lactamase inhibitors
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A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure–activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid.
- Yusof, Yusralina,Tan, Daniel T.C.,Arjomandi, Omid Khalili,Schenk, Gerhard,McGeary, Ross P.
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supporting information
p. 1589 - 1593
(2016/07/27)
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- ORALLY EFFECTIVE ANTI-HYPERTENSIVE AGENTS
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Novel thiolester compounds are disclosed which are orally effective angiotensin converting enzyme inhibitors useful in the treatment of mammalian hypertension. They have the formula, EQU1 wherein Z denotes-B-A 2, R 1 is H or an acyl group, A 1 is a carboxylic acid containing at least one amino or imino-N-, A 2 is a carboxylic acid containing at least one amino or imino-N-or a lower alkyl ester or amide thereof, B is a 2-4 carbon backbone chain in mercapto linkage to S which includes a carbonyl or sulfonyl group joined in carboxamido or sulfonamido linkage, respectively, to A 2. Preferably A 2 includes a 4-6 membered C-N ring or a 5 membered ring of one N, one S and 3 C atoms.
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- PROLINE DERIVATIVES AND RELATED COMPOUNDS
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New proline derivatives and related compounds which have the general formula STR1 are useful as angiotensin converting enzyme inhibitors.
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