Jomthonic Acid A, a Modified Amino Acid from a Soil-Derived Streptomyces

Abstract

Jomthonic acid A (1), a new modified amino acid, was isolated from the culture broth of a soil-derived actinomycete of the genus Streptomyces. The structure and absolute configuration of 1 were determined by spectroscopic analyses and chemical conversion. Jomthonic acid A (1) induced differentiation of preadipocytes into mature adipocytes at 2-50 μM.

Characterization of the Jomthonic Acids Biosynthesis Pathway and Isolation of Novel Analogues in Streptomyces caniferus GUA-06-05-006A

“…According to these observations, it seems reasonable to propose the transfer by AT 1 of 2-methyl-2-eno-butyryl-CoA (MEB-CoA) as the carboxylic acid incorporated by JomP1 (Figure 3). Furthermore, a certain degree of flexibility of AT 1 could explain the biosynthesis of other JAs previously described [42,43]. In this hypothetical model, no role can be envisaged for the JomP1 KR domain.…”

“…The chemical structure of 1 and 2 corresponded to novel analogues of JA A, a previously identified natural product with adipogenic activity produced by Streptomyces sp. BB47 [42]. Structurally, JA A (peak 3 , UPLC R t = 5.209 min, m / z 388.2141[ M + H] + (calculated for C 22 H 30 NO 5 388.2118)), consists of a βMePhe residue with its amino and carboxyl group attached to a short polyketide chain and to a hydroxyacid unit, respectively (Figure 2B).…”

“…This has enabled the identification of three novel metabolites belonging to the jomthonic acid (JA) family of NPs. Up to date, only three members (JA A–C) of this family of molecules have been reported [42,43]. We describe the isolation and structural determination of two new JA A derivatives, and the identification of additional potential related compounds.…”

Simamycin (5′-O-geranyluridine): a new prenylated nucleoside from Streptomyces sp.

“…2,3 In our screening for structurally unique or rare secondary metabolites from Streptomyces, we isolated plant hormone-like spiroacetals of polyketide origin, 4 a linear polyketide δ-lactone with antimetastatic property, 5 macrocyclic polyketides with a biosynthetically unprecedented heterocyclic ring structure 6 and methylphenylalanine derivatives with adipocyte differentiation promoting activity. 7 Further attempts to obtain new bioactive compounds from Streptomyces, a soil-derived strain TP-A0872, was chosen for chemical investigation, which led to the isolation of a new geranylated nucleoside, simamycin (1; Figure 1). …”

Nocapyrones: α- and γ-Pyrones from a Marine-Derived Nocardiopsis sp.

“…Thus, the development of side effect-free new agents for type 2 diabetes is desperately desired. In our screening program for discovering new lead scaffolds for adiponectin inducers from natural products [17,18,19], a marine-derived Nocardiopsis strain was found to produce a new α-pyrone ( 1 ) along with three known γ-pyrones, nocapyrones B, H, and L ( 2 – 4 , Figure 1). Interestingly, nocapyrone L ( 4 ) was isolated as an enantiomeric mixture, which is noticeable in marine natural products.…”