Metabolic Engineering of Methylotrophic Bacteria for Conversion of Methanol to Higher Value Added ProductsEPA Grant Number: R826729
Title: Metabolic Engineering of Methylotrophic Bacteria for Conversion of Methanol to Higher Value Added Products
Investigators: Lidstrom, Mary E. , Dien, Steven Van
Current Investigators: Lidstrom, Mary E.
Institution: University of Washington
EPA Project Officer: Richards, April
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $190,000
RFA: Technology for a Sustainable Environment (1998) RFA Text | Recipients Lists
Research Category: Sustainability , Pollution Prevention/Sustainable Development
Description:The goal of this project is to develop an optimized strain for converting methanol into higher value added products, by directed metabolic engineering of a methylotrophic bacterium, Methylobacterium extorquens AM1. The hypothesis to be tested is that energy metabolism can be optimized and carbon flux can be directed to specific metabolic branches by manipulating formaldehyde production and consumption pathways. The importance of this work is the potential for using such strains in industry to shift away from non-renewable, petrochemical-based feedstocks to non-polluting bioprocesses based on renewable feedstocks.
Approach:The approach for this project is to address three key problems that stand as barriers to the general use of methylotrophs in bioprocesses: lack of understanding of metabolic flux through methylotrophic branches; lack of specific expression systems for manipulating enzyme activities; lack of optimized, high density fermentation processes for recombinant strains. Each of these problems will be addressed as follows: 1. Apply techniques of metabolic modeling to direct experimental approaches for understanding carbon flux through each of the major metabolic branches of methylotrophy. The goal of this work is to develop testable models for optimizing energy production and for redirection of metabolic flux to increase production of a specific target product. 2. Develop regulated expression systems and use these to manipulate pathways for making, polybetahydroxybutyrate (PHB). The goals of this work are to develop tools for metabolic engineering and to demonstrate the utility of the modeling approach for directed metabolic engineering with an environmentally-important product (biodegradable plastic). 3. Develop high density fermentation capabilities for recombinant strains. The goal of this work is to provide information on optimizing production capabilities for these strains.
Expected Results:The expected results of this project will be the development of a series of strains for converting methanol to higher value added products, as well as the development of tools (vectors and models) that can be used in subsequent years to tailor-make production strains for specific products. The goal of this three-year project is to develop the platform strain and use PHB as the model product for testing the platform. The result should be a versatile system suitable for widespread use.
Improvements in Risk Management: The ability to produce chemicals and materials from a renewable resource in an environmentally benign fashion will substantially reduce both short-term and long-term risks associated with current chemical production and manufacturing facilities.