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Collaborative Research: SusChEM: Engineering the thermotolerant yeast Kluyveromyces marxianus for the synthesis of biobased chemicals

合作研究：SusChEM：改造耐热酵母马克斯克鲁维酵母用于合成生物基化学品

基本信息

批准号：
1803677
负责人：
Nancy Da Silva
金额：
$ 31.5万
依托单位：
University of California-Irvine
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1803677&HistoricalAwards=false
关键词：
Collaborative Research SusChEM Engineering thermotolerant

项目摘要

This project seeks to develop the yeast Kluyveromyces marxianus as a platform microorganism for industrial biomanufacturing. A critical area of the US industrial biotechnology sector is the conversion of biomass and other renewable feedstocks to high value and commodity chemicals. K. marxianus can grow at high temperature in high acidity, and on a wide range of different sugars. These are important traits for economic bioprocesses. The project will develop new genetic engineering tools for this yeast and apply these tools to engineer the bio-production of two important classes of chemicals that are traditionally produced from petroleum feedstocks. The project will also contribute to the training of graduate and undergraduate students, as well as the development of new educational outreach programs for high school and community college students from diverse backgrounds.The overall goal is to establish K. marxianus as a platform host for the production of a broad range of biobased chemicals. Critical to advancing K. marxianus is the development of new synthetic biology tools that can rapidly create strains with multiple genome edits and that can accurately control transcription of native and heterologous genes. This project addresses these challenges by (1) developing new enabling tools and methods for rapid strain development and genome engineering in this yeast species, and (2) applying the tools for metabolic engineering of pathways leading to commercially significant native (acetate esters) and non-native (polyketide) products. Phenylethyl and isoamyl acetate are valuable fragrance/flavor compounds and are used as industrial solvents. Polyketides have significant value as pharmaceuticals, including as antibiotic, anticancer, and cholesterol-lowering drugs. The rationale behind this project is that K. marxianus is a highly promising microbial host for non-aseptic (and aseptic) bioprocesses that can convert a range of different sugars into high-value and industrially-relevant chemicals and proteins. This research is transformational because it develops new synthetic biology tools and metabolic engineering approaches to harness and enhance the native traits of K. marxianus, enabling new bioprocesses for the conversion of renewable feedstocks to valuable products.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

本项目致力于将马尔克逊克鲁维酵母开发为工业生物制造的平台微生物。美国工业生物技术部门的一个关键领域是将生物质和其他可再生原料转化为高价值和大宗商品化学品。马氏克氏杆菌能在高温、高酸度和多种不同的糖类上生长。这些都是经济生物过程的重要特征。该项目将为这种酵母开发新的基因工程工具，并应用这些工具来设计两种重要化学物质的生物生产，这两种化学物质传统上是从石油原料中生产的。该项目还将有助于对研究生和本科生的培训，以及为来自不同背景的高中生和社区大学生开发新的教育推广计划。总体目标是将K.marxanus建立为生产各种生物基础化学品的平台东道主。发展马氏克氏杆菌的关键是开发新的合成生物学工具，这些工具可以快速创建具有多基因组编辑的菌株，并可以准确控制本地和异源基因的转录。该项目通过以下方式解决这些挑战：(1)开发在该酵母物种中快速菌株开发和基因组工程的新的使能工具和方法，以及(2)将这些工具应用于代谢工程的途径，从而获得具有商业意义的本地(醋酸酯)和非本地(聚酮)产品。乙酸苯乙酯和乙酸异戊酯是有价值的香料/风味化合物，用作工业溶剂。聚酮类化合物具有重要的药用价值，包括作为抗生素、抗癌和降胆固醇药物。这个项目背后的理论基础是，K.marxanus是一个非常有前途的微生物宿主，可以在非无菌(和无菌)生物过程中将一系列不同的糖转化为高价值和与工业相关的化学品和蛋白质。这项研究具有变革性，因为它开发了新的合成生物学工具和新陈代谢工程方法，以利用和增强K.marxanus的本地特征，使可再生原料转化为有价值的产品的新生物过程成为可能。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。