Award Abstract # 1935354
A foundational platform to engineer synthetic heterotrophy in yeast

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: TRUSTEES OF TUFTS COLLEGE
Initial Amendment Date: August 22, 2019
Latest Amendment Date: August 22, 2019
Award Number: 1935354
Award Instrument: Standard Grant
Program Manager: Steven Peretti
speretti@nsf.gov
 (703)292-4201
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: December 1, 2019
End Date: November 30, 2022 (Estimated)
Total Intended Award Amount: $323,320.00
Total Awarded Amount to Date: $323,320.00
Funds Obligated to Date: FY 2019 = $323,320.00
History of Investigator:
  • Nikhil Nair (Principal Investigator)
    Nikhil.Nair@tufts.edu
Recipient Sponsored Research Office: Tufts University
80 GEORGE ST
MEDFORD
MA  US  02155-5519
(617)627-3696
Sponsor Congressional District: 05
Primary Place of Performance: Tufts University
200 College Ave, SEC 242
Medford
MA  US  02155-6013
Primary Place of Performance
Congressional District:
05
Unique Entity Identifier (UEI): WL9FLBRVPJJ7
Parent UEI: WL9FLBRVPJJ7
NSF Program(s): Cellular & Biochem Engineering
Primary Program Source: 01001920DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1757
Program Element Code(s): 149100
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

Baker's yeast is an important organism for producing ethanol and complex bioproducts, but it can use only a limited number of carbon sources. A variety of renewable and/or cheap carbon sources are currently available. Expanding the capacity of baker's yeast to use these sources to produce bioproducts would be beneficial. The investigators will attempt to discover the mechanisms that control carbon utilization in yeast. Design principles will then be developed to help expand the range of carbon sources that can be used. This will expand the production of renewable fuels and chemicals. Graduate and undergraduate students will participate in this research. They will also be engaged in community outreach efforts to enhance the visibility of the work to the larger community.

Non-native substrates represent a significant fraction of renewable and inexpensive feedstocks. Little work has been done to explore the benefits of integrating cellular regulatory control over heterologous assimilation pathways. Therefore, goal of this work is to 1) demonstrate that cellular decision-making when used to couple growth-related processes with non-native substrate assimilation has significant benefits in generating strains of baker?s yeast that can rapidly grow on any number of structurally diverse substrates, and 2) that these insights can be leveraged to develop a universal platform to engineer and optimize growth on non-native substrates. The platform developed here will also enable functional genomics studies to identify modulators of non-native substrate metabolism in a manner not possible in the past. It is anticipated that the outcomes from the project will extend beyond baker's yeast and the substrates that are the focus of this project since the paradigm developed here is expected to aid similar efforts with other industrially relevant microbes.

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.

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

To realize a sustainable bioeconomy, chemicals and fuels must be produced from renewable and cheap raw materials. Inedible plant and agricultural biomass (e.g., stems, roots, leaves) are highly desirable for this purpose since they are abundant, cheap, and inedible. Further, they are often burned to generate energy or composted and if used as feed for biomanufacturing, could generate substances of significantly higher value. In biomanufacturing, E. coli and baker?s yeast (Saccharomyces cerevisiae) are the most well-established cellular systems used to generate useful chemicals from plant biomass. However, neither of these two single celled organisms can utilize all components that make up inedible plant biomass. The work conducted under this NSF grant supported developing novel strains of baker?s yeast that have been engineered to use several of the sugars derived from inedible biomass that they naturally do not consume. Further, the goal of the work was to understand the genetic basis for how to rapidly engineer this yeast to consume sugars that are ?unnatural? to it.

  Through our work, we found various surprising outcomes. First, we found that this yeast was highly adaptable to consuming new sugars, which is contrary to the well-accepted paradigm. Through our work, we found that the key is to ?trick? this yeast into thinking the new non-natural sugars are highly preferred sugars (i.e., altering the yeast?s perception such that it thinks a new substrate is one that it really likes). Using this approach, we were able to show that this yeast can rapidly utilize a single or multiple of these non-native sugars. Further, we found that many of the traditional engineering approaches used to engineer this yeast may be unnecessary or counterproductive. Specifically, extensive engineering that is undertaken through traditional approaches leads to strains that are hobbled in other natural functions, such as resilience to stresses. This is important since strains used for biomanufacturing must be resilient to stresses associated with large scale manufacturing operations. Thus, through our work, we were able to demonstrate that this yeast can be readily and rapidly engineered to utilize a number of different biomass-derived sugars and provided a minimalistic, yet holistic approach, which minimizes genetic alterations to maintain high robustness of this yeast for future biomanufacturing applications. 

 


Last Modified: 02/01/2023
Modified by: Nikhil U Nair

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