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.

该项目旨在开发酵母Kluyveromyces Marxianus，作为一种用于工业生物制造的平台微生物。美国工业生物技术部门的关键领域是生物量和其他可再生原料的转化为高价值和商品化学品。 K. marxianus可以在高酸度和各种不同的糖中在高温下生长。这些是经济生物过程的重要特征。该项目将为该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的化学物质的生物生产，这些化学物质传统上是由石油原料生产的。该项目还将为研究生和本科生的培训做出贡献，以及针对来自不同背景的高中和社区大学生的新教育外展计划的开发。总体目标是建立K. Marxianus作为生产广泛生物基化学品的平台主持人。对于推进K. Marxianus至关重要的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个基因组编辑的菌株，并且可以准确控制天然和异源基因的转录。该项目通过（1）开发新的启用工具和方法来解决这些酵母菌物种快速劳累开发和基因组工程的方法，以及（2）应用工具，用于途径的代谢工程，从而导致商业意义的本机（醋酸酯）和非本地（Polyketide）产品。苯甲基和乙酸异戊酯是有价值的香气/风味化合物，被用作工业溶剂。聚酮化合物具有与药物一样重要的价值，包括作为抗生素，抗癌和降低胆固醇的药物。该项目背后的理由是，K。marxianus是非精神分裂（和无菌）生物过程的高度有希望的微生物宿主，可以将一系列不同的糖转换为高价值和工业相关的化学物质和蛋白质。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代谢工程方法来利用和增强K. Marxianus的本地特征，从而使可再生原料的转换为有价值的产品促进了新的生物处理，以使NSF的法定任务反映了通过评估的构成群体的构成群体的范围，并反映出了该奖项的范围。