Recent Patents on Biotechnology - Volume 8, Issue 1, 2014

Calanolides are naturally occurring pyranocoumarins found particularly in Calophyllum species (family Clusiaceae/ Guttiferae), and are well known for their potent anti-human immunodeficiency virus (HIV) activity. Various preclinical and clinical studies with this class of compounds are going on, and the National Cancer Institute (NCI) has been playing an active and supportive role in this regard. The present review covers an up-to-date literature of naturally occurring calanolides in view of their anti-HIV potential and total syntheses including information on related patents.

The number of botanical dietary supplements in the market has recently increased primarily due to increased health awareness. Standardization and quality control of the constituents of these plant extracts is an important topic, particularly when such ingredients are used long term as dietary supplements, or in cases where higher doses are marketed as drugs. The development of fast, comprehensive, and effective untargeted analytical methods for plant extracts is of high interest. Nuclear magnetic resonance spectroscopy and mass spectrometry are the most informative tools, each of which enables high-throughput and global analysis of hundreds of metabolites in a single step. Although only one of the two techniques is utilized in the majority of plant metabolomics applications, there is a growing interest in combining the data from both platforms to effectively unravel the complexity of plant samples. The application of combined MS and NMR in the quality control of nutraceuticals forms the major part of this review. Finally I will look at the future developments and perspectives of these two technologies for the quality control of herbal materials.

Withania somnifera Dunal is one of the most commonly used plants in Ayurvedic and indigenous system of medicine in India for over thousands of years. In view of its varied therapeutic potential, the plant has also been the subject of considerable scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactones built on an intact or rearranged ergostane framework, in which C22 and C26 are oxidized to form a six-member lactone ring. In recent years, numerous pharmacological investigations have been carried out utilizing W. somnifera extracts and several patents have been filed on pharmacological and medicinal importance of withanolides and extracts of W. somnifera, individually or in combination. Considering the immense importance of withanolides for medicinal purposes, the establishment of strategies to improve withanolides yield are highly desirable. Under natural conditions, W. somnifera possesses restricted levels of withanolides then, alternatives for obtaining withanolides in better yields are imperative. In vitro approaches followed by metabolic engineering could be attractive tools to achieve this goal. Therefore, we present here an overview of the development of various protocols for in vitro tissue regeneration from W. somnifera and in vitro secondary metabolite production as well. The review also gives an account of selected patents on various important activities of phytochemicals and extracts of W. somnifera.

The use of plants for healing diseases is one of the oldest medical practices and there are several studies showing that botany and medicine are related. Recent researches have shown that around 25% of new chemical entities and 42% of anticancer drugs marketed worldwide from 1981 to 2006 are obtained from natural products and their derivatives. One-third of the botanical biodiversity of the planet is in South American tropical ecosystems (Neotropical). Over the centuries, plants have been used by indigenous people for curing diseases. This strong tradition has been a great challenge for the scientific community in order to validate the folkloric medicinal use of herbs. In this way, a very few Neotropical pharmaceutical products have reached the market in industrialized countries, even though they have a considerable plant diversity. Plants synthesize several organic compounds which are not related to their growth and development and are called secondary metabolites or natural products that are derived from central or primary metabolism. Because plants are sessile organisms, they have to respond quickly to environmental changes in order to escape and survive under unfavorable conditions. Drought is one of the most worldwide serious impediments for crop yields producing adverse negative effects on plant growth, by impacting leaves and roots growth, stomatal conductance, photosynthetic rate and biomass gain. The three major classes of secondary metabolites are produced from pathways of different primary metabolites, including glycolysis, tricarboxilic acid cycle, aliphatic amino acids, pentose phosphate pathway, shikimate pathway and aromatic amino acids. This review compiles the metabolic changes occurring at primary metabolite level and total biosynthesis of natural products with potential for the development of new drugs in response to drought.

Arabidopsis thaliana is the first model plant, the genome of which has been sequenced. In general, intensive studies on this model plant over the past nearly 30 years have led to many new revolutionary understandings in every single aspect of plant biology. Here, we review the current understanding of anthocyanin biosynthesis in this model plant. Although the investigation of anthocyanin structures in this model plant was not performed until 2002, numerous studies over the past three decades have been conducted to understand the biosynthesis of anthocyanins. To date, it appears that all pathway genes of anthocyanins have been molecularly, genetically and biochemically characterized in this plant. These fundamental accomplishments have made Arabidopsis an ideal model to understand the regulatory mechanisms of anthocyanin pathway. Several studies have revealed that the biosynthesis of anthocyanins is controlled by WD40-bHLH-MYB (WBM) transcription factor complexes under lighting conditions. However, how different regulatory complexes coordinately and specifically regulate the pathway genes of anthocyanins remains unclear. In this review, we discuss current progresses and findings including structural diversity, regulatory properties and metabolic engineering of anthocyanins in Arabidopsis thaliana.

Plants are capable of producing a myriad of chemical compounds. While these compounds serve specific functions in the plant, many have surprising effects on the human body, often with positive action against diseases. These compounds are often difficult to synthesize ex vivo and require the coordinated and compartmentalized action of enzymes in living organisms. However, the amounts produced in whole plants are often small and restricted to single tissues of the plant or even cellular organelles, making their extraction an expensive process. Since most natural products used in therapeutics are specialized, secondary plant metabolites, we provide here an overview of the classification of the main classes of these compounds, with its biochemical pathways and how this information can be used to create efficient in and ex planta production pipelines to generate highly valuable compounds. Metabolic genetic engineering is introduced in light of physiological and genetic methods to enhance production of high-value plant secondary metabolites.

Nature is an irrefutable source of inspiration for the modern man in many aspects. The observation and understanding of nature have allowed the development of new materials, new sources of energies, new drugs etc. Specifically, natural products provide a great contribution to the development of new agents for the treatment of infections and antitumor agents. However, obtaining natural products directly from animals, fungi, bacteria, plants etc has been considered not enough to attend the high demand by pharmaceutical industries. In this regard, various strategies based on biotechnological processes or synthetic approaches have been developed. In this scenario the total synthesis can be undoubtedly a useful and powerful tool for obtaining higher amounts of natural products and/or structural modifications thereof. Herein, we emphasize successful examples of total synthesis of galanthamine, morphine, paclitaxel and podophyllotoxin - natural products approved as pharmaceuticals.

There is a consensus that plants are great sources of metabolites with a broad variety of functions. This is particularly important because plants cannot run away from environmental conditions that can threat their existence. The numerous biological activities exhibited by plant natural products prompted humanity to use such substances or their derivatives for the treatment and/or prevention of diseases. The more we know the flora around the world the higher is the chance to find new lead compounds for the design of more potent drugs or nutraceuticals. This review first deals with Brazilian flora, contextualizing the most studied medicinal species and related patents. It also describes a compilation of relevant works based on the use of stress conditions to enhance the biosynthesis of valuable metabolites in cell cultures, tissue cultures (hairy roots) and whole plants by using native or crop plants around the world.

Artemisinin, a potent antimalarial natural products isolated from aerial parts of Artemisia annua L. Many patents have been reported that the demand for artemisinin is exponentially increasing year after year due to increased incidences of drug resistant malaria throughout the world. Leaf explants were used frequently as target tissue to generate transgenic of Artemisia. annua L. However, obtaining a large number of transgenic lines through out the year is a laborious and delicate process. To circumvent this, we have developed a highly efficient leaf explant based Agrobacterium mediated transformation of A. annua L. plant. The gus gene was used as screenable marker to assess and optimize the performance of T-DNA delivery. The age of explant, kind of bacterial inoculation, suspension duration, infection times and co-culture conditions were optimized. The co-culture was carried out with Agrobacterium tumefaciens strain EHA105 under desiccation condition in the dark at 25-28 0C for 2-4 days. Complete analysis of transgene insertion demonstrated that the optimized method of transformation from leaf explants of A. annua L. was efficient and highly reproducible.