Pfalz M.,Max Planck Institute for Chemical Ecology |
Pfalz M.,University Paris - Sud |
Mikkelsen M.D.,Copenhagen University |
Mikkelsen M.D.,Evolva Inc. |
And 4 more authors.
Plant Cell | Year: 2011
Indole glucosinolates, derived from the amino acid Trp, are plant secondary metabolites that mediate numerous biological interactions between cruciferous plants and their natural enemies, such as herbivorous insects, pathogens, and other pests. While the genes and enzymes involved in the Arabidopsis thaliana core biosynthetic pathway, leading to indol-3- yl-methyl glucosinolate (I3M), have been identified and characterized, the genes and gene products responsible for modification reactions of the indole ring are largely unknown. Here, we combine the analysis of Arabidopsis mutant lines with a bioengineering approach to clarify which genes are involved in the remaining biosynthetic steps in indole glucosinolate modification. We engineered the indole glucosinolate biosynthesis pathway into Nicotiana benthamiana, showing that it is possible to produce indole glucosinolates in a noncruciferous plant. Building upon this setup, we demonstrate that all members of a small gene subfamily of cytochrome P450 monooxygenases, CYP81Fs, are capable of carrying out hydroxylation reactions of the glucosinolate indole ring, leading from I3M to 4-hydroxy-indol-3-yl-methyl and/or 1-hydroxy-indol-3-yl-methyl glucosinolate intermediates, and that these hydroxy intermediates are converted to 4-methoxyindol- 3-yl-methyl and 1-methoxy-indol-3-yl-methyl glucosinolates by either of two family 2 O-methyltransferases, termed indole glucosinolate methyltransferase 1 (IGMT1) and IGMT2. © 2011 American Society of Plant Biologists. Source
Jensen N.B.,Copenhagen University |
Jensen N.B.,University of British Columbia |
Zagrobelny M.,Copenhagen University |
Hjerno K.,University of Southern Denmark |
And 5 more authors.
Nature Communications | Year: 2011
For more than 420 million years, plants, insects and their predators have co-evolved based on a chemical arms race including deployment of refined chemical defence systems by each player. Cyanogenic glucosides are produced by numerous plants and by some specialized insects and serve an important role as defence compounds in these intimate interactions. Burnet moth larvae are able to sequester cyanogenic glucosides from their food plant as well as to carry out de novo biosynthesis. Here we show that three genes (CYP405A2, CYP332A3 and UGT33A1) encode the entire biosynthetic pathway of cyanogenic glucosides in the Burnet moth Zygaena filipendulae. In both plants and insects, convergent evolution has led to two multifunctional P450 enzymes each catalysing unusual reactions and a glucosyl-transferase acting in sequence to catalyse cyanogenic glucoside formation. Thus, plants and insects have independently found a way to package a cyanide time bomb to fend off herbivores and predators. © 2011 Macmillan Publishers Limited. All rights reserved. Source
Lee J.Y.,University of Michigan |
Lee J.Y.,Evolva Inc. |
Passalacqua K.D.,University of Michigan |
Passalacqua K.D.,Emory University |
And 2 more authors.
PLoS ONE | Year: 2011
Background: Bacillus anthracis produces two catecholate siderophores, petrobactin and bacillibactin, under iron-limited conditions. Here, we investigate how variable iron and oxygen concentrations influence the biosynthetic output of both siderophores in B. anthracis. In addition, we describe the differential levels of transcription of select genes within the B. anthracis siderophore biosynthetic operons that are responsible for synthesis of petrobactin and bacillibactin, during variable growth conditions. Methodology/Principal Findings: Accumulation of bacillibactin in B. anthracis Sterne (34F2) and in a mutant lacking the major superoxide dismutase (ΔsodA1) was almost completely repressed by the addition of 20 μM of iron. In contrast, petrobactin synthesis in both strains continued up to 20 μM of iron. Accumulation of petrobactin and bacillibactin showed a slight increase with addition of low levels of paraquat-induced oxidative stress in wild type B. anthracis Sterne. Cultures grown with high aeration resulted in greater accumulation of petrobactin relative to low aeration cultures, and delayed the repressive effect of added iron. Conversely, iron-depleted cultures grown with low aeration resulted in increased levels of bacillibactin. No difference was found in overall superoxide dismutase (SOD) activity or transcriptional levels of the sodA1 and sodA2 genes between iron-depleted and iron-replete conditions at high or low aeration, suggesting that SOD regulation and iron metabolism are separate in B. anthracis. The highest transcription of the gene asbB, part of the petrobactin biosynthetic operon, occurred under iron-limitation with high aeration, but transcription was readily detectable even under iron-replete conditions and in low aeration. The gene dhbC, a member of the bacillibactin biosynthetic operon, was only transcribed under conditions of iron-depletion, regardless of growth aeration. Conclusion: These data suggest that bacillibactin regulation is highly sensitive to iron-concentration. In contrast, although regulation of petrobactin is less dependent on iron, it is likely subject to additional levels of regulation that may contribute to virulence of B. anthracis. © 2011 Lee et al. Source
News Article | August 21, 2015
REINACH, Switzerland--(BUSINESS WIRE)--Evolva (SIX: EVE) announces the launch of nootkatone, a highly prized citrus flavour and fragrance (F&F) ingredient. By brewing nootkatone from sugar, rather than extracting it from the skin of grapefruits, Evolva’s process allows nootkatone to be made in large amounts in a highly reproducible, contaminant free, sustainable and affordable manner. Evolva has now begun selling nootkatone as a F&F ingredient to food, beverage, personal care, and home care product producers around the world. Nootkatone is a natural aroma ingredient that occurs in grapefruit and certain other plants. It is responsible for the characteristic smell of grapefruit. With a record of demonstrated safety, it is approved in all major countries for use in F&F, and is used in a wide range of foods, drinks, and skin care products. However, until now, its use has been limited by its high price, limited supply, product quality, and other factors. But nootkatone’s commercial prospects go significantly beyond F&F. In both laboratory and field studies, nootkatone has demonstrated excellent activity against biting and nuisance pests, notably the ticks that are responsible for spreading Lyme disease , but also mosquitoes, head lice, bed bugs and other pests. Earlier this year Evolva therefore submitted a request to the US Environmental Protection Agency (EPA) to classify nootkatone as a biochemical pesticide active ingredient (a subcategory of biopesticide). Such a classification allows for a potentially expedited process for registration of nootkatone for use against pests. Evolva received approval of this request on 19th August, and will now engage in an estimated 2-3 years of regulatory work to get nootkatone approved as an insect and tick repellent in the USA. Evolva is also investigating other geographies. Nootkatone’s revenue and bottom line impact on Evolva will initially be modest and the launch does not affect Evolva’s financial projections for 2015. Revenues and net income are expected to increase significantly from 2016 onwards. Until final EPA approval is obtained, all revenues in the USA at least will come from F&F applications. “Nootkatone is one of Evolva’s most exciting products, ”Evolva CEO Neil Goldsmith said. “Since we are committed to improving public health through better functional ingredients, we are doing our part to ensure that nootkatone reaches its full potential—responsibly, but expeditiously.” Evolva is a pioneer and global leader in sustainable, fermentation-based approaches to ingredients for health, wellness and nutrition. Evolva’s products include stevia, resveratrol, vanillin, nootkatone and saffron. As well as developing its own proprietary ingredients, Evolva also deploys its technology for partners, providing them with a competitive edge and sharing in the returns they make. For more information see www.evolva.com. Questions about our fermentation approach? Have a look at our video. Information about the EPA classification system for biopesticides can be found here. Most people develop Lyme disease from the bite of an immature tick, which is tiny (less than 2 mm across), difficult to see, and as a result often goes completely unnoticed. Information about ticks and how to identify them can be found here. Recent information about the spread of Lyme Disease in the USA can be found here. Information from the US Centers for Disease Control and Prevention on tick repellents including nootkatone can be found here. This press release contains specific forward-looking statements, e.g. statements including terms like believe, assume, expect or similar expressions. Such forward-looking statements are subject to known and unknown risks, uncertainties and other factors which may result in a substantial divergence between the actual results, financial situation, development or performance of the company and those explicitly or implicitly presumed in these statements. Against the background of these uncertainties readers should not place undue reliance on forward-looking statements. The company assumes no responsibility to update forward-looking statements or to adapt them to future events or developments.
News Article | May 11, 2015
MINNEAPOLIS & REINACH, Switzerland--(BUSINESS WIRE)--Evolva and Cargill have agreed to begin the engineering phase for converting an existing Cargill manufacturing facility to produce next-generation stevia sweeteners (steviol glycosides). The ingredients are expected to be commercially available in 2016. Stevia-based sweeteners are highly sought-after natural, zero-calorie sweeteners. However, their broader use is currently constrained by their taste at high usage levels, which can be bitter or have an after-taste. Certain stevia sweetener molecules such as Reb D and Reb M do not have this problem, but, because they only make up a tiny portion of the plant’s leaf (much less than 1 percent), it is prohibitively costly to obtain them from the stevia plant. Fermentation removes these constraints and should allow a dramatic expansion in the use of next generation stevia sweeteners, allowing food and beverage producers to create new classes of lower calorie products that taste great and are affordable to all. These sweeteners will be produced in a Cargill fermentation system in Blair, Nebraska. Using a larger existing facility gives the companies the flexibility to expand rapidly and cost-effectively to meet commercial demand. Under terms of the 2013 joint development agreement between the two companies, Evolva received an option to obtain up to a 45% stake in the business to commercialize the sweeteners. Evolva has informed Cargill that it intends to exercise this 45% option, subject to final terms being agreed between the two companies. Total investment by Cargill and Evolva in the engineering phase will be USD 3 million. Evolva does not expect to incur further costs relating to the option exercise before the final agreement is in place, which is expected to be in the second half of 2015. Upon signing the final agreement Evolva anticipates that it will need to invest low tens of millions USD through 2017. Evolva is exploring various financing options in this context. Per the 2013 agreement, if Evolva and Cargill cannot finalize terms on the option exercise, Evolva will receive royalty payments from global sales of the steviol glycoside products; these royalties will scale from mid-single digit to low double-digit percentages as a function of sales volume and other parameters. In this circumstance Cargill would repay Evolva’s share of the engineering costs. Evolva CEO Neil Goldsmith commented, “We have been delighted by our close cooperation with Cargill over the past two-plus years. The decision to commence engineering work reflects our mutual desire and commitment to bring great tasting, cost-effective sweeteners to the market as soon as possible. While there remain risks which could impact the timing of the final product launch and consumer uptake, we are confident in our joint progress.” "Adding new production capabilities at our Cargill Blair facility fits strategically with our overall growth plan and is an exciting and necessary step as we prepare for the commercialization of a next-generation sweetener,” stated David Henstrom, vice president for Health Ingredients at Cargill. “This sweetener will offer a new, delicious choice for reduced and zero-calorie food and beverages." Cargill provides food, agriculture, financial and industrial products and services to the world. Together with farmers, customers, governments and communities, we help people thrive by applying our insights and nearly 150 years of experience. We have 145,000 employees in 67 countries who are committed to feeding the world in a responsible way, reducing environmental impact and improving the communities where we live and work. For more information, visit Cargill.com and our News Center. Evolva is a pioneer and global leader in sustainable, fermentation-based approaches to ingredients for health, wellness and nutrition. Evolva’s products include stevia, vanillin, saffron and resveratrol. As well as developing its own proprietary ingredients, Evolva also deploys its technology for partners, providing them with a competitive edge and sharing in the returns they make. For more information see www.evolva.com. Questions about our fermentation approach? Have a look at our video. This press release contains specific forward-looking statements, e.g. statements including terms like believe, assume, expect or similar expressions. Such forward-looking statements are subject to known and unknown risks, uncertainties and other factors which may result in a substantial divergence between the actual results, financial situation, development or performance of the company and those explicitly or implicitly presumed in these statements. Against the background of these uncertainties readers should not place undue reliance on forward-looking statements. The company assumes no responsibility to update forward-looking statements or to adapt them to future events or developments.