Optimization of a yeast platform for large scale production of hexadecanol and octadecanol. Phase I application.

脂肪醇是工业上用作表面活性剂、乳化剂、软化剂和润滑剂的有价值的化合物。它们也广泛用于个人护理产品。脂肪醇形成了一个价值26.4亿美元的全球产业，大部分产量来自亚洲。两种广泛使用的脂肪醇，十六醇和十八醇是由棕榈油的化学转化得到的。虽然棕榈油转化技术已经成熟，但将其用于化学生产仍存在问题。这包括与食品工业争夺棕榈油，以及棕榈种植园扩张导致的森林砍伐和生物多样性丧失。此外，棕榈衍生产品受到价格和供应波动的影响。用于生产这些醇的微生物发酵平台可以绕过这些问题，提供经济和环境效益。为了开发生产十六醇和十八醇的替代来源，我们已经改造了酵母菌株，通过发酵糖或纤维素水解产物来生产这些化学品。选择酵母作为生产平台，因为它是稳健的，可以耐受工业规模的发酵条件，并且可以利用各种各样的原料。在4升规模的发酵试验中，每升培养物产生高达200 mg的脂肪醇。使用纤维素水解产物作为原料的发酵每升培养物产生高达95毫克的脂肪醇。此外，我们已经能够改造菌株，以便专门生产十八醇。本项目的目标是（1）进行进一步的菌株工程，以提高脂肪醇的产量。这将包括将生产系统转移到Yarrowia lipolytica中，Yarrowia lipolytica是一种已知能产生和积累大量脂质的酵母。(2)实现750升规模的发酵，以确定工业规模生产的工艺，并生产和纯化足够的产品，以允许十六醇和十八醇的潜在消费者在自己的应用中测试我们的产品。实现这些目标将产生一个可靠的成本竞争力的脂肪醇来源，将有利于加拿大的工业和减少与脂肪醇生产的环境影响。

Fatty alcohols are valuable compounds used industrially as surfactants, emulisifiers, emollients and lubricants. They are also extensively used in personal care products. Fatty alcohols form a $2.64 billion global industry with the bulk of production coming from Asia. Two widely used fatty alcohols, hexadecanol and octadecanol are derived from the chemical conversion of palm oil. While the technology for palm oil conversion is well established there are problems with its use for chemical production. These include competition for palm oil with the food industry and the deforestation and loss of bio-diversity driven by expansion of palm plantations. Additionally, palm derived products suffer from price and supply volatility. A microbial fermentation platform for production of these alcohols could bypass these problems providing both economic and environmental benefits. To develop an alternative source for the production of hexadecanol and octadecanol we have engineered a yeast strain to produce these chemicals by fermentation of sugar or cellulosic hydrolysates. Yeast was chosen as a production platform as it is robust, can tolerate industrial scale fermentation conditions and can utilize a wide variety of feed stocks. Fermentation trials at a four litre scale yield up to 200mg of fatty alcohol per litre of culture. Fermentations using cellulosic hydrolysates as feed stock yield up to 95mg of fatty alcohol per litre of culture. Additionally, we have been able to engineer the strain so as to exclusively produce octadecanol. The objectives of this project are (1) to perform further strain engineering to increase fatty alcohol production. This will include moving the production system into Yarrowia lipolytica, a yeast known to produce and accumulate large amounts of lipids. (2) To achieve fermentations at 750 litre scale to both define a process for industrial scale production and to produce and purify sufficient product to allow potential consumers of the hexadecanol and octadecaol to test our product in their own applications. Realization of these objectives will yield a reliable cost competitive source of fatty alcohols that will benefit Canadian industries and reduce the environmental impact associated with fatty alcohol production.