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How Gene-Edited Insects Are Providing Food, Fuel and Waste Disposal

2023-09-02 21:52:52
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Insects have been making commercial inroads as feed for poultry, fish, pigs, cattle and even pet food, though, for now, it remains a niche product. Biotech tools, however, are allowing breeders to ramp up insect production, and with new investment, their approach is gaining traction.

In the last several years, companies producing black soldier flies (BSF, or Hermetia illucens) and mealworms (Tenebrio molitor) have raised forged ahead, paving the way for insect products to reach European and Asian markets. Insect factories are expanding, and some companies are applying gene editing to improve protein quality and speed up hatching and growth. If the momentum continues to build, the insect protein market is forecast to grow $1.14 billion by 2027.

In Israel, a consortium of insect-based animal feed companies backed by the Israel Innovation Authority was set up in January, bringing them together with researchers using machine learning and fly genomics to optimize and scale up BSF production and the insects’ nutritional profile. The companies — Entoprotech, FreezeM, Ambar, Shachar, NRGene, NeoManna, BugEra and Rafael Feed Mills — are joined by academic researchers from five academic institutes, all of whom are editing genes in the fly genome sequence to enhance breeding.

Part of the consortium is FreezeM, based in Nachshonim. The startup was set up by three Weizmann Institute of Technology doctoral graduates, who developed a technology that induces neonatal larvae into suspended animation to extend shelf life for shipment purposes. It is a “paused larvae” stage obtained through environmental conditions, says Yuval Gilad, FreezeM co-founder and CEO, and just as with hibernation, it is reversible.

FreezeM has also turned to CRISPR–Cas9 to improve the nutritional content of BSF strains. The company has deployed 400 CRISPR–Cas9 guide RNAs to target about 150 genes that control metabolism, which yielded strains with bigger larvae, a longer larval period and increased resilience under stress.

One of the genes they've edited is a key regulator of molting from larva to pupa, which, when tweaked, yields larvae 50 percent larger than an unedited one. Other genes worth targeting would be those controlling chitin, the hard polysaccharide that makes up insects’ exoskeleton. A reduction in chitin would prove valuable for optimizing aquaculture feed, says Idan Alyagor, FreezeM co-founder and chief technology officer.

Another Israeli company, BugEra, a startup from Ben Gurion University, is genetically engineering strains of black soldier for use as biofuel. Fly maggots are rich in lipids that could provide a sustainable alternative to crop oils. Another advantage is that BSF farming could tap into circular economy opportunities. “BSF can be reared on different substrates, like food waste and manure,” says Yoav Etgar, CEO and co-founder of the Beer Sheva-based biotech. Fly oil, however, has yet to take off commercially because, so far, the market has leaned towards feed production, says Anna Melkov, BugEra chief technology officer and co-founder.

To overcome this bias, BugEra has developed a BSF strain with double the lipid content, using the CRISPR–Cas9 gene-editing technique to modify genes involved in fat metabolism. Because identifying flies with desirable mutations is time intensive and can become a bottleneck, BugEra developed a technique that allows DNA extraction and screening of hundreds of individuals per day. The startup also expects to add a phenotypic marker such as eye color to accelerate screening further, as well as gene downregulation techniques, such as RNA interference (RNAi), to broaden the characteristics of BSF lines.

Meanwhile, the UK insect genetics company Beta Bugs focuses on selecting strains with the best traits for breeding. The company scientists at the facility, located at the Roslin Innovation Centre near Edinburgh, start by collecting physical and environmental insect parameters from their insect populations, selecting for increased larval biomass, faster development and greater number of eggs laid. This approach allows them to disentangle favorable genetics from possible environmental variables: “We can be assured that our insects’ performance is increasing not because they received more food, or were reared in a higher temperature, but because we are improving the underlying genetics,” says Thomas Farrugia, the company’s CEO. Beta Bugs ships BSF lines to customers in the insect farming industry.

To support the industry’s expansion, Beta Bugs recently co-founded the UK’s Insect Bioconversion Association, in conjunction with BSF company Better Origin and other commercial insect producers. Their goal is to raise awareness of the role insect farming can play in reducing food waste while providing high-quality animal feed, oils and fertilizer. They also work to expedite the regulatory pathway through engagement with the U.K. government.

A type of beetle larva commonly called a mealworm is also part of the surging interest in bug farms. Beta Hatch produces mealworms (the larvae of Tenebrio molitor) for use as feed in aquaculture and farm animal nutrition, as well as pet food. “The potential for insects in the food supply chain is immense,” says entomologist Virginia Emery, who is founder and CEO of Beta Hatch. Beyond providing high-quality nutrients for animal feed and plant fertilizer, larvae in the Tenebrionidae are remarkable for their digestive powers, which include plastic waste biodegradation. “The only known way to biodegrade Styrofoam is in the gut of a mealworm,” says Emery, adding that worms can digest and eliminate harmful mycotoxins and process all kinds of waste.

Beta Hatch deploys genomic tools to raise their bugs in the most efficient and scalable way possible. Through selective breeding, the scientists map key traits such as weight and development time, tracking their heritability, and monitoring the genomic diversity of their breeding stock. In addition, Beta Hatch is developing a CRISPR proof-of-concept toolkit to produce custom proteins in their insects.

Another mealworm farm with products on the market is Ÿnsect. Its protein ingredient is already in U.S. luxury dog food brand Bernie’s, among others, and is exported around the world for use in pet food or to feed fish, to fertilize plants and for human consumption. The Paris-based company was founded in 2011 by four scientists and environmental activists with a vision to produce an alternative, sustainable product for feed and food. They set up vertical insect farms powered by robotics, each yielding several tons of mealworm products a year, and in 2021, the European food safety authority deemed mealworms safe for human consumption.

In June 2023 Ÿnsect launched the world’s first high-density gene chip for insect breeding. The chip contains 679,205 single-nucleotide polymorphisms, covering more than 99 percent of the mealworm’s coding regions. It can help scientists identify genes linked to traits of interest, such as growth performance, reproduction, or disease resistance. The company plans to make the new chip, called AxiomYNS_Mol1, available to the wider scientific community to help users decipher biological pathways, answer fundamental questions or improve selection of mealworm lines with desired traits.

All in all, with the work of these companies and genetic editing tools, insect farming is gaining ground in the global food economy as an alternative source of animal protein.

This article is reproduced with permission and was first published on August 11, 2023.

参考译文
基因编辑昆虫如何提供食物、燃料和垃圾处理
昆虫正逐步进入家禽、鱼类、猪、牛乃至宠物饲料的商业领域,尽管目前昆虫仍属于小众产品。然而,生物技术工具使育种者能够大幅提高昆虫的产量,随着新投资的进入,这种趋势正逐渐获得关注。在过去的几年中,生产黑水虻(Hermetia illucens)和黄粉虫(Tenebrio molitor)的公司不断前进,为昆虫产品进入欧洲和亚洲市场铺平了道路。昆虫工厂正在扩张,一些公司甚至开始应用基因编辑技术以提高蛋白质质量并加速孵化和生长。如果这种趋势持续下去,预计到2027年,昆虫蛋白市场将达到11.4亿美元。在以色列,一个由以色列创新局支持的昆虫动物饲料公司联盟于1月份成立,这些公司与研究人员合作,利用机器学习和果蝇基因组学优化并扩大黑水虻的生产及营养成分。联盟的成员公司包括Entoprotech、FreezeM、Ambar、Shachar、NRGene、NeoManna、BugEra和Rafael饲料厂,它们与来自五所学术机构的科研人员一起,正在对果蝇基因组进行编辑以改善育种。联盟的一部分是位于Nachshonim的FreezeM公司。该初创公司由三位魏茨曼科学研究所的博士毕业生创立,他们开发了一项技术,将新生幼虫置于休眠状态以延长其保质期并便于运输。FreezeM联合创始人兼首席执行官Yuval Gilad表示,这种“暂停幼虫”的状态是通过环境条件实现的,就像冬眠一样,是可以逆转的。FreezeM还利用CRISPR-Cas9技术来提升黑水虻的营养成分。公司已部署了400条CRISPR-Cas9引导RNA,以靶向控制代谢的大约150个基因,从而培育出体型更大的幼虫、更长的幼虫期以及在压力下更高的抗性。他们编辑的其中一个重要基因是控制幼虫蜕皮为蛹的关键调节基因。对这一基因的优化可使幼虫体积比未优化的增加50%。另一些值得关注的基因是那些控制几丁质的基因,几丁质是一种构成昆虫外骨骼的硬质多糖。FreezeM联合创始人兼首席技术官Idan Alyagor表示,减少几丁质含量对于优化水产养殖饲料将非常有价值。另一个以色列公司BugEra是一家由本·古里安大学孵化的初创企业,正在对黑水虻进行基因改造,以用作生物燃料。蝇蛆富含脂质,可以作为作物油的一种可持续替代品。另一个优势是,黑水虻养殖可以利用循环经济机会。“黑水虻可以在不同的基质上饲养,比如食品废弃物和粪便,”位于贝尔谢巴的生物科技公司BugEra的首席执行官兼联合创始人Yoav Etgar表示。然而,BugEra首席技术官兼联合创始人Anna Melkov表示,蝇油尚未在商业上取得突破,因为到目前为止市场更倾向于饲料生产。为了克服这种偏见,BugEra使用CRISPR-Cas9基因编辑技术,改造了脂肪代谢相关的基因,培育出脂质含量翻倍的黑水虻品系。由于寻找具有理想突变的蝇类耗时较长,BugEra开发了一种技术,每天可以提取并筛查数百个个体的DNA。该公司还计划添加表型标记,例如眼色,以进一步加速筛选过程,并采用基因下调技术,如RNA干扰(RNAi),以拓宽黑水虻品系的特性。与此同时,英国的昆虫基因公司Beta Bugs专注于选择最佳品系进行育种。位于爱丁堡附近罗斯林创新中心的公司科学家首先从昆虫种群中收集物理和环境参数,选择那些具有更高幼虫生物量、更快的发育速度和更多产卵量的个体。这种方法使他们能够区分出优良基因与可能的环境变量:“我们能够确保昆虫表现的提升不是因为它们获得了更多食物,或饲养在更高温的环境中,而是因为我们正在改善其基础基因,”公司首席执行官Thomas Farrugia表示。Beta Bugs将黑水虻品系销售给昆虫养殖行业的客户。为了支持该行业的扩展,Beta Bugs最近与黑水虻公司Better Origin及其他商业昆虫生产商共同成立了英国昆虫生物转化协会。他们的目标是提高人们对昆虫养殖在减少食品浪费、提供高质量动物饲料、油脂和肥料作用的认识。他们也通过与英国政府的合作,推动监管流程的加快。另一种被称为黄粉虫的甲虫幼虫,也成为了人们对昆虫农场兴趣激增的一部分。Beta Hatch公司生产黄粉虫(Tenebrio molitor的幼虫),供水产养殖、家畜饲养及宠物食品使用。“昆虫在食品供应链中的潜力是巨大的,”该公司的创始人兼首席执行官、昆虫学家Virginia Emery表示。除了为动物饲料和植物肥料提供高质量的营养之外,鞘翅目昆虫的幼虫还以强大的消化能力著称,包括塑料垃圾的生物降解。“目前唯一已知能生物降解发泡胶的方式,是通过黄粉虫的肠道,”Emery补充道,并指出黄粉虫可以消化并去除有害的霉菌毒素,还能处理各种废弃物。Beta Hatch利用基因组工具以最高效和可扩展的方式养殖昆虫。通过选择性育种,科学家们追踪关键性状(如体重和发育时间)的遗传性,并监测其育种材料的基因组多样性。此外,Beta Hatch正在开发一种基于CRISPR技术的概念验证工具包,以在昆虫中产生定制蛋白。另一家在市场上已有产品的黄粉虫农场是Ÿnsect。其蛋白质原料已经出现在美国高端宠物食品品牌Bernie’s等产品中,并出口至世界各地,用于宠物食品、鱼类饲料、植物肥料和人类消费。这家总部位于巴黎的公司于2011年由四位科学家和环保活动家创立,他们的愿景是生产可持续的替代品,用于饲料和食品。他们建立了由机器人驱动的垂直昆虫农场,每个农场每年可产出数吨的黄粉虫产品。2021年,欧洲食品安全局认定黄粉虫对人类消费是安全的。2023年6月,Ÿnsect推出了全球首个高密度昆虫育种基因芯片。该芯片包含679,205个单核苷酸多态性,覆盖了黄粉虫超过99%的编码区。它可以帮助科学家识别与关键特征(如生长性能、繁殖或抗病性)相关的基因。公司计划将其命名为AxiomYNS_Mol1的新芯片提供给更广泛的科学界,以帮助研究人员解析生物通路,回答基础问题,或改善黄粉虫优良品系的选择。总而言之,随着这些公司的努力和基因编辑工具的应用,昆虫养殖正在全球食品经济中作为动物蛋白的替代来源逐渐取得一席之地。本文经授权转载,最初发表于2023年8月11日。
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