Anhydromevalonolactone

Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties.[Pubmed:34768863]

Int J Mol Sci. 2021 Oct 22;22(21):11432.

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria Streptomyces sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain Streptomyces sp. SH-1312 with addition of mix metals (Co(2+) + Zn(2+)) ions at 0.5 mM in Gause's medium. Under these conditions, the stress metabolite Anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC(50) value of 19.65 +/- 5.7 microg/mL in DPPH, IC(50) of 15.49 +/- 4.8 against NO free radicals, the IC(50) value of 19.65 +/- 5.22 microg/mL against scavenging ability, and IC(50) value of 19.38 +/- 7.11 microg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC(50) values of 35.81 +/- 4.2 microg/mL after 24 h, 23.29 +/- 3.8 microg/mL at 48 h, and 16.25 +/- 6.5 microg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.

Poly(isoprenecarboxylates) from Glucose via Anhydromevalonolactone.[Pubmed:27933217]

ACS Macro Lett. 2016 Oct 18;5(10):1128-1131.

A short and efficient synthesis of a series of isoprenecarboxylic acid esters (ICAEs) and their corresponding polymers is presented. The base-catalyzed eliminative ring-opening of Anhydromevalonolactone (3) provides isoprenecarboxylic acid (6-H), which was further transformed to the ICAEs. Reversible addition-fragmentation chain-transfer (RAFT) polymerization was used to synthesize high molecular weight (>100 kg mol(-1)) poly(isoprenecarboxylates) with dispersities (D) of ca. 1.5. The glass transition temperatures (T(g)) and entanglement molecular weights (M(e)) of the poly(isoprenecarboxylates) were determined and showed similar trends to the T(g) and M(e) values for analogous poly(acrylate esters). These new glucose-derived materials could provide a sustainable alternative to poly(acrylates).

Assessing medium constituents for optimal heterologous production of anhydromevalonolactone in recombinant Aspergillus oryzae.[Pubmed:25006541]

AMB Express. 2014 Jun 27;4:52.

Anhydromevalonolactone (AMVL) is a bioactive natural product that arises from a molecular biology technique using Aspergillus oryzae as a heterologous host. AMVL has been used as a precursor for the synthesis of insect pest control reagents and has numerous applications in the biotechnological and medical industries. In this study, the Plackett-Burman Design and the Central Composite Design, which offer efficient and feasible approaches, were complemented to screen significant parameters and identify the optimal values for maximum AMVL production. The results suggested that sucrose, NaNO3, yeast extract and K2HPO4 were the key factors affecting AMVL production in a complex medium, whereas the major components required for a defined medium were NaNO3, K2HPO4, KH2PO4 and trace elements. These factors were subsequently optimized using the response surface methodology. Under optimal conditions, a maximum AMVL production of 250 mg/L in the complex medium and 200 mg/L in the defined medium was achieved, which represents an increase of approximately 3-4-fold compared to the commonly used malt extract medium.

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