Bringing novel materials to market to modulate sweet, salt, umami and cooling sensations
将新型材料推向市场以调节甜、咸、鲜和清凉口感
Adire World Health Organization report on the subject of obesity warned, “Overweight and obesity represent a rapidly growing threat to the health of populations in an increasing number of countries. Indeed they are now so common that they are replacing more traditional problems such as undernutrition and infectious diseases as the most significant causes of ill-health.” “We read every day about the link between high levels of sodium in the diet and cardiovascular disease and hypertension,” says Mark Zoller, chief scientific officer of Senomyx, a San Diego, California-based company that employs taste receptor-based assays and screening technologies to discover and develop novel flavors, flavor enhancers and taste modulators for the food, beverage and ingredients industries. The company’s clients in the arenas of savory, sweet, salt and cooling include Ajinomoto, Cadbury, Campbell Soup Company, The Coca-Cola Co., Firmenich SA, Nestlé SA and Solae. “Similarly, there is concern about high levels of calories and sugar in various foods [due to the world’s] growing obesity and diabetes trend,” Zoller adds. “Those are some of the key drivers we picked up on. We’re responding to an industry that is trying to do more in the health and wellness area.”
世界卫生组织关于肥胖问题的报告警告说：“超重和肥胖正日益成为越来越多国家人口健康的严重威胁。事实上，它们现在如此普遍，以至于正在取代营养不良和传染病等传统问题，成为最重大的健康不佳原因。”位于加利福尼亚州圣地亚哥的Senomyx公司首席科学官Mark Zoller表示，该公司采用基于味觉受体的测定和筛选技术，为食品、饮料和配料行业发现和开发新型风味、风味增强剂和口感调节剂。“我们每天都读到饮食中钠含量过高与心血管疾病和高血压之间的关联，”Zoller说。Senomyx公司在咸味、甜味、咸味和清凉口感的领域内的客户包括味之素（Ajinomoto）、吉百利（Cadbury）、金宝汤公司（Campbell Soup Company）、可口可乐公司（The Coca-Cola Co.）、芬美意公司（Firmenich SA）、雀巢公司（Nestlé SA）和索莱公司（Solae）。Zoller补充道：“同样，由于全球肥胖和糖尿病趋势的加剧，人们对食品中高热量和高糖分的担忧也在增加。这些都是我们注意到的一些关键驱动力。我们正在回应一个试图在健康和保健领域做得更多的行业。”
Mark Zoller, Senomyx’s chief scientific officer
马克·佐勒（Mark Zoller），Senomyx公司的首席科学官
Senomyx’s background in the biology of taste took shape in the 1990s with a group of founding academics and entrepreneurs, including Charles Zuker, a professor of biology at the University of California, San Diego. “He was studying the biology of taste and had identified what appeared to be the novel receptors that he predicted were going to be involved in taste,” says Zoller, “but at the time he hadn’t discovered which receptor was responding to which taste.” In founding Senomyx, Zuker teamed with a range of researchers, including Lubert Stryer, professor of cell biology at Stanford University and recipient of a 2007 National Medal of Science; Roger Tsien, Nobel Prize-winning scientist and professor of pharmacology, chemistry and biochemistry at the University of California, San Diego (see sidebar); food chemistry expert and author of “The Curious Cook” Harold McGee, and Denis Baylor, professor emeritus of Neurobiology at Stanford University. (All remain on the company’s scientific advisory board.) “The thought was to use taste receptors to identify novel flavors,” says Zoller. “In the beginning, the idea was to work on both taste and smell, but it turned out that the biology of smell is about 100-times more complicated than that of taste. So the focus of the company soon settled down on taste.”
Senomyx公司在味觉生物学领域的背景始于上世纪90年代，当时由一群创始学者和企业家组成，其中包括加州大学圣地亚哥分校（UCSD）的生物学教授查尔斯·朱克（Charles Zuker）。佐勒说：“他正在研究味觉生物学，并识别出了看似新颖的感受器，他预测这些感受器将参与味觉过程，但当时他还没有发现哪种感受器对应哪种味道。”在创立Senomyx时，朱克与一群研究人员合作，其中包括斯坦福大学生物化学教授、2007年国家科学奖章获得者卢伯特·斯特赖尔（Lubert Stryer）；加州大学圣地亚哥分校药理学、化学和生物化学教授、诺贝尔奖得主罗杰·钱（Roger Tsien）（参见边栏）；食品化学专家、畅销书《好奇的厨师》的作者哈罗德·麦吉（Harold McGee）；以及斯坦福大学神经生物学荣誉教授丹尼斯·贝勒（Denis Baylor）。（他们目前都是公司的科学顾问委员会成员。）佐勒说：“最初的想法是利用味觉感受器来识别新型风味。一开始，我们的目标是同时研究味觉和嗅觉，但后来发现嗅觉的生物学原理比味觉复杂大约100倍。因此，公司的重点很快就集中在了味觉上。”
Discovery and Development
发现与开发
“The key technology that sets us apart from, say, a traditional flavor house is the use of these receptor-based assays,” says Zoller, explaining how the company has over time determined the mechanisms of various receptors. “You could think of it as an artificial taste bud. We know our taste buds have certain cells that respond to many different tastes. What we can do is create a [single taste receptor] system that we can culture and grow in a lab. For example, if we’re looking for a sweet receptor enhancer, we can add various samples to the sweet receptor and then only work on the ones that interact or bind to the [relevant] receptor.” The company has filed a good deal of patents around this key technology. In addition, Senomyx has developed the technology to acquire the various samples under study. “We have a library of both natural and synthetic samples,” says Zoller, estimating the number at around 500,000. “We learned very quickly that we needed to show that the samples we identified in the receptor were having the desired effect,” he continues. “So we then needed to generate a sensory group to be able to study this, much like any flavor house would. In addition, because we needed to see whether these various ingredients functioned in more complex products, we had to develop a product development group. It’s not that we’ll be developing products for our partners, but we needed to show that the things that we’d identifi ed are heat-stable, soluble and have the required physical properties.” The vetted ingredients are then passed along to clients. “I would argue that we’re very complementary to the traditional flavor houses,” he says, “because their expertise is in mixing and putting different flavors together. They’re really experts in ‘how do flavors come together in a flavor mixture, how are they added, what are the various ways in which these products can be manufactured?’ We’re not trying to compete with the fl avor houses. We’re discovering new flavors in new ways. Our expertise is really around that discovery process.”
“将我们与传统香精公司区分开来的关键技术是使用这些基于受体的检测，”佐勒说道，他解释了公司如何随着时间的推移确定了各种受体的机制。“你可以把它想象成一个人工味蕾。我们知道我们的味蕾中有某些细胞会对许多不同的味道做出反应。我们能够做的是创建一个可以在实验室中培养和生长的[单一味觉受体]系统。例如，如果我们正在寻找甜味受体增强剂，我们可以将各种样本添加到甜味受体中，然后只针对那些与[相关]受体相互作用或结合的样本进行研究。”该公司围绕这一关键技术申请了大量专利。此外，Senomyx还开发了获取各种研究样本的技术。“我们拥有自然和合成样本的库，”佐勒说道，估计数量约为50万种。“我们很快就意识到，我们需要证明在受体中识别出的样本具有预期的效果，”他继续说道，“因此，我们需要组建一个感官小组来研究这一点，就像任何香精公司都会做的那样。此外，由于我们需要观察这些不同的成分在更复杂的产品中是否有效，我们还必须组建一个产品开发团队。我们并不是要为我们的合作伙伴开发产品，但我们需要证明我们识别出的成分具有热稳定性、可溶性和所需的物理性质。”经过验证的成分随后会传递给客户。“我认为我们与传统香精公司非常互补，”他说，“因为他们的专长是混合和搭配不同的风味。他们真的是‘风味混合物中风味如何组合、如何添加、这些产品可以通过哪些不同方式制造’方面的专家。我们并不是要与香精公司竞争。我们正在以新的方式发现新的风味。我们的专长就在于这个发现过程。”
Salt and Sweet: Enhancing and Modulating, Not Replacing
盐和甜：增强和调节，而非替代
“By understanding the biochemistry of the taste receptors, our flavors are basically making them more efficient at what they do,” says Zoller. “We’re not making a new sweetener in the case of a sweet enhancer and we’re not making a salt replacer in the case of a salt enhancer. What we aim to do is modulate or enhance the activity of, say, the salt receptor, making it more efficient so that more sodium flows into the taste cell over a given amount of time. And so, [even] with a lowered amount of sodium, that solution will taste just as salty.” The sweet enhancer program has witnessed two key technical achievements since 2007, namely the discovery, identification and vetting of S6973 and S2383. S6973 reportedly allows for an up to 50% reduction in sucrose without sacrifi cing the sweet taste of natural sugar. Development activities are already underway. Senomyx views the material as key to good flavors for healthy formulations. Meanwhile, the company is winding down development activities for S2383, which reportedly allows for a 75% reduction in sucralose without off-tastes or loss of sweet intensity.
“通过了解味觉受体的生物化学机制，我们的风味成分基本上使它们更加高效地发挥作用，”佐勒说道。“在甜味增强剂的情况下，我们并不是在制造新的甜味剂；在盐味增强剂的情况下，我们也不是在制造盐的替代品。我们的目标是通过调制或增强盐味受体等受体的活性，使其更加高效，以便在给定的时间内有更多的钠流入味觉细胞。因此，即使钠含量降低，这种溶液尝起来也会和原来一样咸。”自2007年以来，甜味增强剂项目取得了两项关键的技术成就，即S6973和S2383的发现、识别和验证。据报道，S6973可以在不牺牲天然糖甜味的情况下，将蔗糖减少高达50%。开发活动已经在进行中。Senomyx认为这种材料是健康配方中良好风味的关键。同时，公司正在逐步减少S2383的开发活动，据报道，S2383可以在不产生不良风味或降低甜味强度的情况下，将三氯蔗糖减少75%。
Tsien Wins 2008 Nobel Prize in Chemistry
钱永健获得2008年诺贝尔化学奖
Roger Tsien shares this year’s Nobel Prize in chemistry for his contributions to the work titled “Wavelength mutations and post-translational autoxidation of green fluorescent protein,” published in 1994. Employing a natural tool of some jellyfish, Tsien was able to change the colors of glowing proteins, which allowed them to be tracked during the evaluation of cellular processes. The technique, which has found use in Senomyx’s research, has found medical use in the study of Alzheimer’s disease.
罗杰·钱永健（Roger Tsien）因其在1994年发表的研究“绿色荧光蛋白的波长突变和翻译后自氧化”中的贡献，而获得了本年度的诺贝尔化学奖。通过使用某些水母的自然工具，钱永健能够改变发光蛋白的颜色，这使得在评估细胞过程时能够追踪这些蛋白。这项技术在Senomyx公司的研究中得到了应用，并在阿尔茨海默病的研究中找到了医学用途。
“By understanding the biochemistry of the taste receptors, our fl avors are basically making them more efficient at what they do,” says Mark Zoller, chief scientifi c officer of Senomyx.
Senomyx公司首席科学官马克·佐勒（Mark Zoller）表示：“通过了解味觉受体的生物化学机制，我们的风味成分基本上使它们更加高效地发挥作用。”
In the arena of high-potency sweeteners, the company has screened more than 250,000 natural samples. The goal is to develop novel sweeteners with low or no calories.
在高强度甜味剂领域，该公司已经筛选了超过25万种天然样本。目标是开发低热量或无热量的新型甜味剂。
Savory/Umami 鲜味/美味
Senomyx’s savory program is its most mature. Its goals, Zoller explains, are two-fold: to replace MSG out of concern for health and cost elements, as well as launching new savory ingredients based on an understanding of savory/umami receptors. “Both of these are being applied in the Nestle product development area,” he says. “The flavors are in products. Initially they started in the Pacific Rim and Latin American countries, with the expectation that additional products will be launched over the course of the coming year on a rolling basis.”
Senomyx公司的鲜味计划是其最成熟的计划。佐勒解释说，其目标有两个：一是出于对健康和成本因素的考虑，替换味精（MSG）；二是基于对鲜味/美味受体的理解，推出新的鲜味成分。“这两者都在雀巢的产品开发领域中得到了应用，”他表示。“这些风味已经添加到产品中。它们最初在太平洋地区和拉丁美洲国家推出，预计在未来一年中，将陆续推出更多产品。”
Blocking Bitter
阻挡苦味
Senomyx’s efforts to improve the healthiness of foods and beverages go beyond the reduction of problem ingredients—they also involve the improvement of the flavor of nutritious, but inherently bitter, ingredients. To this end, the company has partnered with soy protein supplier Solae to block/modulate the bitterness of hydrolyzed soy protein while minimizing the addition of sugar, fat or salt. “It’s a very healthy source of protein and could be used to a greater extent if it wasn’t for the taste,” says Zoller. Solae is betting that these blockers will speed up consumer acceptance of foods containing soy protein, including beverages, energy bars and infant formula. According to the agreement’s announcement, “Solae will have exclusive worldwide use of the flavor ingredients in virtually all categories of foods and beverages that contain added soy protein. Solae will fund the discovery and development of these flavor systems, and Senomyx will be entitled to certain milestone and royalty payments based on sales of Solae products containing any flavor ingredients developed under the agreement.”
Senomyx公司改善食品和饮料健康性的努力不仅仅局限于减少问题成分——它们还涉及改善营养丰富但本身具有苦味的成分的口感。为此，该公司与大豆蛋白供应商Solae公司合作，以在最小化添加糖、脂肪或盐的同时，阻止/调节水解大豆蛋白的苦味。“大豆蛋白是一种非常健康的蛋白质来源，如果可以改善它的味道，它将会被更广泛地使用，”Zoller说道。Solae公司认为，这些阻滞剂将加速消费者对含有大豆蛋白的食品（包括饮料、能量棒和婴儿配方奶粉）的接受度。根据协议公告，“Solae公司将在几乎所有含有添加大豆蛋白的食品和饮料类别中独家使用这些风味成分。Solae公司将为这些风味系统的发现和开发提供资金，而Senomyx公司将有权根据销售含有根据协议开发的任何风味成分的Solae产品获得一定的里程碑和版税支付。”
Senomyx’s electrophysiology screening.
Senomyx的电生理学筛选。
Cooling Agents
冷却剂
In many cases, due to confidentiality issues, Senomyx is unable to discuss specifics in terms of which companies are allied with which projects. However, in January of this year Senomyx president and CEO Kent Snyder announced a cooling agent collaboration with Firmenich. “Annual sales of current cooling compounds are in the $400 million range,” he noted at the time. “We estimate the opportunity of flavor systems incorporating approved cooling agents may be three to four times this size.” Under the three-year deal, Senomyx is conducting its taste receptor discovery activities under its Cool Flavor banner, making available any of the resulting (viable) cooling agents to Firmenich, exclusively. Firmenich is paying research fees and additional payments when undisclosed milestones are met. Firmenich will address manufacturing, marketing and sales of any cooling flavor systems. “Upon commercialization,” Snyder noted, “Senomyx will receive royalty payments based on sales of products containing new flavor ingredients developed under the agreement. This allows us to optimize the commercial potential of our cooling agents by collecting royalties on the sales of the flavor systems, rather than just the cooling compounds.” “Many [existing cooling] agents have deficiencies that restrict their utility, such as weak cooling characteristics, bitter off-taste, burning and tingling sensations, unwanted odor, limited solubility, and non-proprietary status,” he added. “We believe that greater solubility, stability in high temperatures and a wide pH range could increase the number of applications for the cooling agents.”
在很多情况下，由于保密问题，Senomyx 无法具体讨论哪些公司与哪些项目结盟。然而，在今年一月份，Senomyx 的总裁兼首席执行官 Kent Snyder 宣布了与 Firmenich 在冷却剂方面的合作。他当时指出，“当前冷却化合物的年销售额在 4 亿美元左右。我们估计，包含已批准的冷却剂的风味系统的机会可能是这一数字的三到四倍。”根据为期三年的协议，Senomyx 在其“Cool Flavor”的旗帜下开展味觉受体发现活动，将任何由此产生的（可行的）冷却剂独家提供给 Firmenich。Firmenich 支付研究费用，并在达到未公开的里程碑时支付额外费用。Firmenich 将负责任何冷却风味系统的制造、营销和销售。“商业化后，”Snyder 指出，“Senomyx 将根据销售含有根据协议开发的新风味成分的产品收取特许权使用费。这将使我们能够通过销售风味系统的特许权使用费来优化我们冷却剂的商业潜力，而不仅仅是冷却化合物。”他补充说，“许多现有的冷却剂存在限制其效用的缺陷，例如冷却特性弱、苦味、灼烧和刺痛感、不良气味、溶解度有限和非专有地位。我们认为，提高冷却剂在高温度下的溶解度和稳定性以及广泛的 pH 范围可以增加冷却剂的应用数量。”
Senomyx employs taste receptor-based assays and screening technologies to discover and develop novel flavors, flavor enhancers and taste modulators for the food, beverage and ingredients industries.
Senomyx 利用基于味觉受体的分析和筛选技术，为食品、饮料和配料行业发现和开发新型风味、风味增强剂和味觉调节剂。
“The Cool Flavor program is a little bit different from our others in that we decided that, because of the nature of cooling agents and how they’re used in different product areas, it made sense to work with a single partner, Firmenich,” says Zoller. “That’s quite different from our other programs where the various programs are divided by the various receptor targets and applications and different product areas.”
“Cool Flavor 项目与其他项目略有不同，因为我们决定，由于冷却剂的特性和它们在不同产品领域的应用方式，与单一合作伙伴 Firmenich 合作是有意义的，”Zoller 表示。“这与我们的其他项目完全不同，因为各种项目是根据不同的受体目标、应用领域和产品领域进行划分的。”
New Frontiers
新领域
While many of Senomyx’s future endeavors are proprietary, Zoller did agree to discuss several innovations that may shape the company’s future work. In 2007, Senomyx announced it had possibly discovered the primary protein receptor responsible for human salt taste: SNMX-29. “We’ve initiated, using this receptor, the identification of salt taste enhancers,” says Zoller. “That was a very interesting series of studies. Through the analysis of all these different proteins that are in taste buds, we’ve identified some additional proteins that look like they could be taste receptors for something else. This is some of the exploratory work that we’re doing that may be part of the programs of the future.”
虽然 Senomyx 的许多未来工作都是专有的，但 Zoller 还是同意讨论一些可能影响公司未来工作的创新。2007 年，Senomyx 宣布可能发现了负责人类咸味感知的主要蛋白质受体：SNMX-29。“我们已经利用这种受体，开始了咸味增强剂的识别工作，”Zoller 说。“这是一系列非常有趣的研究。通过对味蕾中所有这些不同蛋白质的分析，我们已经确定了一些额外的蛋白质，它们看起来可能是其他物质的味觉受体。这是我们正在进行的一些探索性工作，可能会成为未来项目的一部分。”
