This glossary defines some commonly used terms in the world of perfume and fragrance. We will add to it when new terminology is introduced in the industry. Processed by means of enfleurage, alcohol extraction or steam distillation. ACCORD: A combination of raw materials blended together to find the proper balance and effect a perfumer desires when creating a fragrance.
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- Synthetic biology strategies for microbial biosynthesis of plant natural products
- Festive tasting notes decoded: Christmas spices in your wine?
- Scent of Danger: Are There Toxic Ingredients in Perfumes and Colognes?
- BUTTER AND DAIRY SPREADS
- The Taste Makers
- What is ambergris?
- FlavorDB: a database of flavor molecules
- General Perception of Liposomes: Formation, Manufacturing and Applications
- Website access code
Synthetic biology strategies for microbial biosynthesis of plant natural productsVIDEO ON THE TOPIC: Aroma Chemicals for Creating Perfume - 1 to 5
Sign up to take part. A Nature Research Journal. Metabolic engineers endeavor to create a bio-based manufacturing industry using microbes to produce fuels, chemicals, and medicines. Plant natural products PNPs are historically challenging to produce and are ubiquitous in medicines, flavors, and fragrances. Engineering PNP pathways into new hosts requires finding or modifying a suitable host to accommodate the pathway, planning and implementing a biosynthetic route to the compound, and discovering or engineering enzymes for missing steps.
In this review, we describe recent developments in metabolic engineering at the level of host, pathway, and enzyme, and discuss how the field is approaching ever more complex biosynthetic opportunities.
The field of metabolic engineering endeavors to create a green manufacturing industry based on bioproduction of commodity chemicals in cell factories. Plant natural products PNPs are especially important targets because of their utility as flavors, fragrances, and medicines, but can be challenging to synthesize due to stereochemical complexity.
PNPs are produced via specialized plant metabolism involving numerous enzymes from diverse classes that enzymatically transform central metabolites into secondary metabolite compounds such as the analgesic morphine and antimalarial artemisinin.
Many PNPs are obtained from processed plant biomass, requiring substantial land, water, and time investment, and which introduces insecurity in supply chains due to variability in crop yields resulting from pests or extreme weather. Furthermore, intermediates in a PNP biosynthetic pathway are often unavailable from the host plant, thus complicating efforts to produce novel derivatives of the PNP of interest. Microbial production of PNPs can overcome these challenges by enabling 1 on-demand production capabilities associated with microbial cells, 2 scalable and controlled production in fermentation facilities, and 3 the capacity to produce PNPs and PNP intermediates at higher purity or yield than those provided by the native plant host.
In addition, microbial production of PNPs can serve as a discovery platform to synthesize novel derivatives of PNPs and gain insight into enzymes involved in plant secondary metabolism. Metabolic engineering to produce a particular PNP relies on iterative engineering cycles of design, build, and test referred to as the DBT cycle 1. At the level of the host, DBT includes selection and engineering of the host to overproduce PNP-precursor metabolites in sufficient quantity; at the pathway level, a biosynthetic route to produce the PNP is determined and candidate enzymes are tested or discovered; and at the enzyme level, protein engineering may be warranted to improve function or produce derivative compounds Fig.
Metabolic engineering at multiple levels has enabled engineering of increasingly complex heterologous PNP pathways. Labels show product name or compound utility. Advances in synthetic biology and enabling technologies like DNA synthesis 2 , sequencing 3 , and analytical techniques 4 have accelerated the DBT cycles for metabolic and protein engineering to the point where both can be deployed to engineer the biosynthesis of a particular molecule.
Indeed, the complexity of PNP pathways being discovered and engineered has steadily increased over the past 20 years Fig. Heterologous PNP biosynthesis and application of DBT require judicious selection and engineering of the production host, the biosynthetic pathway, and the individual enzymes composing the pathway. In this review we discuss recent examples and technologies that enable engineering of hosts, pathways, and enzymes to make PNPs and novel PNP derivatives and the technological advances on the horizon that are expected to further accelerate this field.
In the coming years, we expect researchers to increasingly employ metabolic and protein engineering to solve a range of ever more complex biosynthetic challenges.
A PNP may be selected as a metabolic engineering target for a variety of reasons including medicinal utility, industrial application, or scientific interest. For a given PNP, the first step towards heterologous production is selection of an appropriate host species in which to engineer the pathway. Within a species, use of previously developed strains that overproduce necessary metabolites can greatly accelerate progress.
And lastly, within a given strain, preliminary engineering of the host prior to incorporation of heterologous enzymes can facilitate implementation of the non-native pathway in a new context. When selecting a host species for a heterologous pathway, properties such as ease of cloning, ease of culturing, and suitability of the host for the new enzymes and compounds are considered. Organisms with a long history of use in research, and particularly in metabolic engineering, often have well developed techniques for cloning, culturing, and industrial scale-up that make them attractive choices.
A first choice of host for production of PNPs may be plant cells, where plant specific subcellular compartments and protein processing are conserved, a topic recently reviewed elsewhere 7.
Indeed, model plants such as Nicotiana benthamiana are useful for transient expression of plant pathway enzymes during preliminary testing and discovery, as enzyme function, necessary cofactors, and substrate pools are likely to be maintained in planta 8 , 9.
However genetic manipulation of plants, even well-established model plants, remains unwieldy and slow compared to microorganisms and thus a microbial host is often preferable. Other microorganisms are often employed to purposes which evolution has made them especially well-suited: Streptomyces is often used for the production of antibiotics originally derived from Streptomyces species 10 ; Corynebacterium glutamicum is widely used for the high-titer production of amino acids 11 ; Yarrowia lipolytica is frequently employed when using lipids as a substrate Yet for most applications involving the production of PNPs in a microbial host, E.
Thus, the most immediate question for a metabolic engineer seeking to produce a compound in a heterologous host is often whether to use E. Distinct advantages of S. Some enzymes from PNP biosynthesis pathways, such as cytochrome Ps, are transmembrane proteins and require the presence of an appropriate membrane, such as the endoplasmic reticulum ER , for proper anchoring and folding.
This potential roadblock was demonstrated during the Semi-synthetic Artemisinin Project, a landmark achievement in metabolic engineering in which S. In this project, both E. High activity of this enzyme could not be attained in E. While strategies exist to modify transmembrane proteins for function in the cytosol 15 , using S.
Furthermore, S. Conversely, E. For example, the presence of a native pathway for certain isoprenoid compounds was used to engineer E. One additional avenue when choosing a host organism for PNP biosynthesis is to utilize multiple organisms in a co-culture with components of a metabolic pathway split between distinct organisms of the same or different species 18 , 19 , 20 , In one example, benzylisoquinoline alkaloids BIAs were synthesized in an E.
In another example, high titers of an anthocyanin PNP were achieved by splitting the metabolic burden of the pathway across four E. Following selection of a host species, engineering the host to increase titers of native metabolites that are biosynthetic precursors to the product of interest can greatly facilitate downstream production of PNP molecules. The core metabolic networks of model organisms are well-characterized and can be used to guide overexpression and knockout modifications for overproduction of central metabolite precursors and to address common challenges e.
One of the advantages of biosynthesis over chemical synthesis is how readily biosynthetic strains are distributed; once a strain has been engineered to produce a compound, researchers looking to expand on that work in the future need not repeat tedious syntheses of starting material. Strains of E. Platform strains that overproduce central metabolites or a heterologous secondary metabolite can both be useful: central metabolites, such as geranyl pyrophosphate or amino acids, provide a starting point for the production of potentially thousands of diverse PNP compounds, while secondary metabolites can provide an easy starting point from which to engineer biosynthesis of a specific PNP product.
For example, platform strains that produce the key branch point alkaloid S -reticuline 22 , 23 have enabled microbial biosynthesis of a wide range of BIAs produced by Papaver somniferum opium poppy , including morphine 24 and noscapine Likewise, strictosidine producing strains 26 provide a key branch point metabolite for the biosynthesis of monoindole alkaloids MIAs , which include vincristine, ibogaine, yohimbine, and thousands of others.
A platform strain can be useful not only because it produces a valuable starting material, but also because the means of production of said starting material are particularly inexpensive, sustainable, or offer easy handling for the researcher or industrial producer. This is demonstrated by the engineering of an efficient simultaneous saccharification and co-fermentation SSCF strain for bioethanol production in E. In another example, an enzyme was designed that allows for assimilation of formate into central metabolism 28 , potentially allowing the biosynthesis of medicines and commodity chemicals from formate, which is expected to be abundantly available from electrochemical reduction of CO 2.
Lastly, researchers generated a strain of E. Although there is significant interest in utilizing natural photosynthesizing microorganisms e.
While the aforementioned strains have not yet been used for the production of PNPs, the other PNP-producing strains discussed throughout this review could potentially be integrated into these platforms to produce complex PNPs de novo from agricultural waste, formate produced with renewable energy 31 , or directly from atmospheric CO 2.
This principle has been demonstrated through the engineering of E. Such strategies could support more sustainable bioprocesses for producing increasingly diverse products, including PNPs, at industrial scale. After selection of a host or existing platform strain, the supply of biosynthetic precursors may be enhanced by modifications to the host, such as gene deletions, swapping of endogenous enzymes with more active homologues, or overexpression of endogenous metabolic genes Fig.
A recent tour de force 33 combined all of these techniques to reprogram yeast central metabolism to overproduce acetyl-CoA for isoprenoid and fatty acid biosynthesis - molecules which are a starting point for many PNPs such as the antimalarial artemisinin.
A model of the yeast reaction stoichiometries for acetyl-CoA, redox cofactors, and sugar was used to determine a more favorable reaction stoichiometry, which was defined as having a reduced ATP requirement, reduced loss of carbon to side reactions, and improved pathway redox balance.
Optimization for tyrosine and p -coumaric acid overproduction, from which many PNPs including some alkaloids, polyphenols, and flavonoids are derived, has also been pursued in the context of E. For example, researchers engineered yeast producing 1. These included engineering feedback-resistant enzymes, over-expressing enzymes at bottlenecks, and removing competing side pathways Deletion of competing or undesired side pathways in the host is a common strategy to increase precursor titers Fig.
In work on the de novo production of strictosidine, a plant-derived alkaloid, researchers monitored biosynthetic intermediates in their engineered pathway to identify competing side pathway Finding that geraniol, an intermediate in strictosidine biosynthesis, was metabolized by the yeast through esterification, deletions were made to ATF1 and OYE2 which reduced undesired host interactions and resulted in a 6-fold increase in strictosidine production.
Finally, evolution has emerged as a powerful approach for host optimization, although it has not yet been directly applied to PNP biosynthesis. In the aforementioned work on altering yeast metabolism from alcoholic fermentation to lipogenesis, researchers also employed laboratory evolution methods to improve lipogenic growth on glucose Deletion of pyruvate decarboxylase genes PDC1, 5, and 6 involved in alcoholic fermentation resulted in strains unable to grow on glucose as a carbon source.
Adaptive laboratory evolution was applied to evolve FFA producing strains lacking ethanol fermentation for growth on glucose by gradually shifting the carbon source from ethanol to glucose over generations. SCRaMbLE utilizes a synthetic yeast chromosome V with recombination sites introduced in all non-essential genes such that when recombination is induced these genes are shuffled within chromosome V.
Following selection of a suitable host, a route to the desired PNP can be planned and implemented. A candidate pathway is first outlined through selection of stepwise chemical intermediates leading from host metabolism to the target compound, followed by selection of enzymes to carry out each specified reaction.
For certain PNPs, detailed knowledge of the native biosynthetic pathway is available and can be used to outline all intermediates and enzymes in a pathway, facilitating pathway engineering into a heterologous host. However, such detailed knowledge can require years or even decades of dedicated research in planta and is frequently unavailable or incomplete.
In such cases, candidate pathway design, enzyme selection, and pathway testing all offer distinct challenges which are discussed in the following sections. Literature on a given PNP biosynthetic route can be instrumental to outlining a pathway, although even for well-studied PNPs there are often gaps in our knowledge.
One way to overcome the restriction of needing plant biochemical data for each enzymatic step is to use an approach agnostic to the natural product in question. When a reaction path to a chemical entity is unknown, retrosynthetic analysis can be used such that the target molecule is transformed into simpler precursor structures without making assumptions about starting material availability. Resulting precursors are in turn transformed into simpler structures until available starting constituents are reached.
By breaking a target molecule into potential precursors, it is then possible to select enzymes which interconvert in the other direction. Of ten available retrosynthesis-based pathway design tools 38 , only RetroPath 39 has been experimentally tested. RetroPath takes starting compounds, a target, and reaction rules to generate potential pathways and was experimentally validated on the design of biosynthetic routes to pinocembrin 40 , a flavonoid four enzymatic steps from E.
If the substrate of the desired reaction is very different from that of the known reaction to which it is being compared, ranking the results by some measure of substrate similarly, such as Tanimoto distance, might be advantageous Retrosynthesis can also be performed manually, without the aid of automated tools. The 10 molecules were a mix of PNPs carvone and vincristine and non-PNPs; the fungal metabolite epicolactone provides an example of a retrosynthetic approach that could be applied to PNPs to identify potential pathways.
The genomic sequence of the native producer of epicolactone was unavailable and so the researchers based their enzymatic retrosynthesis on a previously developed eight-step non-enzymatic chemical synthesis Enzyme classes were assigned to each reaction manually, guided by literature and pathway databases. Multiple enzymes were identified for each of the eight steps based on reaction type, and to narrow down the candidates, enzyme hits were limited to tropolone-like biosynthetic gene clusters identified from the biosynthetic gene cluster databases MIBiG 44 and antiSMASH However, no pathways were experimentally validated within the 90 day time frame.
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Festive tasting notes decoded: Christmas spices in your wine?
Ancient texts and archaeological excavations show the use of perfumes in some of the earliest human civilizations. Modern perfumery began in the late 19th century with the commercial synthesis of aroma compounds such as vanillin or coumarin , which allowed for the composition of perfumes with smells previously unattainable solely from natural aromatics alone. The word perfume derives from the Latin perfumare , meaning "to smoke through". Perfumery, as the art of making perfumes, began in ancient Mesopotamia , Egypt , the Indus Valley Civilization and maybe Ancient China.
Scent of Danger: Are There Toxic Ingredients in Perfumes and Colognes?
We consumers are bombarded with advertisements for natural and organic products. The growing popularity of this belief shows that this subject is in dire need of clarification. The idea that nature can harm us is not new. Have you ever heard of malaria, HIV, tuberculosis, botulism or tetanus? Why, then, are so many convinced that anything and everything natural is healthier for us than synthetic products? It's true that modern chemistry has brought us a number of toxic chemicals, like DDT and dioxins, but do you really think that nature's chemicals are any less harmful to you? In fact, the most toxic chemicals to humans are completely natural! Not only that, but there is much evidence that natural pesticides allowed in organic farming are just as toxic as synthetic pesticides.
BUTTER AND DAIRY SPREADS
It is produced by sperm whales and has been used for centuries, but for many years its origin remained a mystery. Ambergris has been a unique phenomenon for millennia. Fossilised evidence of the substance dates back 1.
Higher revenue in the finished flavors and extracts product lines was offset by lower revenue in certain flavor ingredient product lines. These items were partially offset by the Natural Ingredients business, which reported higher profit compared to the comparable period last year. Fragrance Division sales were CHF 1, million, an increase of 8. Flavour Division sales were CHF 1, million, an increase of 4. Givaudan continued the year with good business momentum and with the project pipeline and win rates being sustained at a high level. This excellent growth was achieved across all product segments and geographies, with our key strategic focus areas of Naturals, Health and well-being, Active Beauty, Integrated Solutions and local and regional customers delivering strong growth, complemented by the recent acquisitions. When measured in local currency terms, the operating income increased by 2. The operating margin decreased to
The Taste Makers
These guidelines are intended to provide a broad framework permitting the development of more specific group or individual standards, according to the requirements of individual countries. Fat spread: A fat spread is a food in the form of an emulsion mainly of the water-in-oil type , comprising principally an aqueous phase and edible fats and oils. Edible fats and oils: Foodstuffs mainly composed of triglycerides of fatty acids. They are of vegetable, animal, milk or marine origin. Tables Restricted zone s may be imposed, with respect to the fat content and to the proportion of milk fat to other types of fat, in accordance with national or other relevant legislation. Concerning the fat content, the IDF standard states that fat spreads shall be classified into three groups, according to the origin of the fat. The name of the food shall be as specified in national legislation.
What is ambergris?
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FlavorDB: a database of flavor molecules
There are thousands of different cosmetic products on the market, all with differing combinations of ingredients. Cosmetics are not a modern invention. Humans have used various substances to alter their appearance or accentuate their features for at least 10, years, and possibly a lot longer.
General Perception of Liposomes: Formation, Manufacturing and Applications
Flavor is an expression of olfactory and gustatory sensations experienced through a multitude of chemical processes triggered by molecules. Beyond their key role in defining taste and smell, flavor molecules also regulate metabolic processes with consequences to health. Such molecules present in natural sources have been an integral part of human history with limited success in attempts to create synthetic alternatives.
Website access code
Each fragrance by Lisa Hoffman has been crafted to capture a destination, feeling, or scent memory. Worldwide shipping is available.
Liposomes are currently part of the most reputed carriers for various molecular species, from small and simple to large and complex molecules. Since their discovery, liposomes have been subject to extensive evolution, in terms of composition, manufacturing and applications, which led to several openings in both basic and applied life sciences. However, most of the advances in liposome research have been more devoted to launching new developments than improving the existing technology for potential implementation.