A New Editor in Chief for Molecules (It's Been a Fun Ride).

It is with mixed feelings that I put fingers to keyboard to write this, perhaps my last Editorial as Editor-in-Chief of Molecules [...].

We've Come a Long Way, Baby: Announcing a Special Issue to Commemorate the Publication of Molecule's 20,000th Paper.

On behalf of my Section Editor-in-Chief co-author colleagues I am pleased to announce a Special Issue to commemorate the recent publication of Molecules' 20,000th paper [...].

Removal of Expression of Concern: Segneanu et al. Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds. Molecules 2015, 20, 22170-22187.

The article [1] published in Molecules was the subject of a law suit related to authorship. We previously published an Expression of Concern to highlight this fact to readers[...].

Molecules New Aims and Scope.

As we approach the end of our 22nd year as the pioneering and preeminent Open Access journal in the field of organic chemistry and natural products, time has come to formally announce what has been the de facto reality of the journal for the past few years, the expansion of the range of topics we cover.[...].

Dr. Kenneth A. Jacobson: First Winner of the Tu Youyou Award, in Honor of the Co-Recipient of the 2015 Nobel Prize in Physiology or Medicine.

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Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin.

Malaria, caused by Plasmodium sp, results in almost one million deaths and over 200 million new infections annually. The World Health Organization has recommended that artemisinin-based combination therapies be used for treatment of malaria. Artemisinin is a sesquiterpene lactone isolated from the plant Artemisia annua. However, the supply and price of artemisinin fluctuate greatly, and an alternative production method would be valuable to increase availability. We describe progress toward the goal of developing a supply of semisynthetic artemisinin based on production of the artemisinin precursor amorpha-4,11-diene by fermentation from engineered Saccharomyces cerevisiae, and its chemical conversion to dihydroartemisinic acid, which can be subsequently converted to artemisinin. Previous efforts to produce artemisinin precursors used S. cerevisiae S288C overexpressing selected genes of the mevalonate pathway [Ro et al. (2006) Nature 440:940-943]. We have now overexpressed every enzyme of the mevalonate pathway to ERG20 in S. cerevisiae CEN.PK2, and compared production to CEN.PK2 engineered identically to the previously engineered S288C strain. Overexpressing every enzyme of the mevalonate pathway doubled artemisinic acid production, however, amorpha-4,11-diene production was 10-fold higher than artemisinic acid. We therefore focused on amorpha-4,11-diene production. Development of fermentation processes for the reengineered CEN.PK2 amorpha-4,11-diene strain led to production of > 40 g/L product. A chemical process was developed to convert amorpha-4,11-diene to dihydroartemisinic acid, which could subsequently be converted to artemisinin. The strains and procedures described represent a complete process for production of semisynthetic artemisinin.

Molecules Best Paper Award 2013.

Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013.

Kilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.

Emulsions of the triterpene squalene ((6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of trans-ß-farnesene ((6E)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process. The scalability of the proposed route was verified by a kilo-scale GMP synthesis. We also report data demonstrating the synthesized semi-synthetic squalene's physical stability and biological activity when used in a vaccine adjuvant formulation.

Approaches and Recent Developments for the Commercial Production of Semi-synthetic Artemisinin.

The antimalarial drug artemisinin is a natural product produced by the plant Artemisia annua. Extracts of A. annua have been used in Chinese herbal medicine for over two millennia. Following the re-discovery of A. annua extract as an effective antimalarial, and the isolation and structural elucidation of artemisinin as the active agent, it was recommended as the first-line treatment for uncomplicated malaria in combination with another effective antimalarial drug (Artemisinin Combination Therapy) by the World Health Organization (WHO) in 2002. Following the WHO recommendation, the availability and price of artemisinin fluctuated greatly, ranging from supply shortfalls in some years to oversupply in others. To alleviate these supply and price issues, a second source of artemisinin was sought, resulting in an effort to produce artemisinic acid, a late-stage chemical precursor of artemisinin, by yeast fermentation, followed by chemical conversion to artemisinin (i.e., semi-synthesis). Engineering to enable production of artemisinic acid in yeast relied on the discovery of A. annua genes encoding artemisinic acid biosynthetic enzymes, and synthetic biology to engineer yeast metabolism. The progress of this effort, which resulted in semi-synthetic artemisinin entering commercial production in 2013, is reviewed with an emphasis on recent publications and opportunities for further development. Aspects of both the biology of artemisinin production in A. annua, and yeast strain engineering are discussed, as are recent developments in the chemical conversion of artemisinic acid to artemisinin.

Developing fermentative terpenoid production for commercial usage.

Terpenoids comprise a large (>55000) family of compounds, very few of which have been used commercially due to low and economically unpractical production in their native hosts (generally plants and microorganisms). Two examples of natural terpenoid production are described (rubber and astaxanthin), but the advent of metabolic engineering has allowed the development of fermentative production processes using heterologous microorganisms. The two biochemical pathways responsible for terpenoid production are described, along with manipulations that enable production of terpenoids at economically viable levels. Finally, this article reviews some terpenoids that are currently in commercial production or development, ranging from semisynthetic production of the antimalarial drug artemisinin, through fragrance molecules, to commodity chemicals such as isoprene and ß-farnesene.

Resumed Publication of Pharmaceuticals in 2009.

After a five year hiatus, we are pleased to announce the resumption of publication of the MDPI journal Pharmaceuticals (ISSN 1424-8247). First launched in 2004, few suitable papers were submitted and only one was published [1], before our limited editorial resources at the time led us to temporarily discontinue publication. Several things have changed since then. First, there has been an explosive growth in the number of manuscripts submitted and published in MDPI's various current journals [2], whose topics clearly fall within the intended scope of Pharmaceuticals and we feel that these manuscripts merit a dedicated forum. Second, the expansion of MDPI, now with Editorial Offices and staff in Basel (Switzerland) and Beijing (China), allows us to provide Pharmaceuticals' authors with all the services they could desire and deserve: a simple manuscript submission process, rigorous peer review, quick revision turnaround, Open Access publication on a new and attractive platform and coverage by all the major abstracting services. In addition, a new Editorial Board comprised of noted academic and industry scientists has been set up for Pharmaceuticals. Finally, to better focus the subject matter published in Pharmaceuticals on molecular medicines, we have also set up a special section in International Journal of Molecular Sciences (IJMS, ISSN 1422-0067) for papers on nutraceuticals or chemopreventives. We look forward to receiving and publishing your papers and as always, we welcome your comments and suggestions. [...].