2008 Annual Report
Abstract
The long-term objective of our proposed studies is the development of a broad-spectrum platform for engineering complexes of metabolic enzymes in bacteria that is expected to dramatically improve the yield of virtually any biosynthetic target produced in microorganisms by accounting for enzyme organization and minimizing metabolic cross-talk. Related studies are currently funded under ONR YIP grant # N000140610565 and focus on the production of 1,2-propylene glycol (1,2-PG). The objective of this particular application is to improve microbial synthesis of D-1,2,4-butanetriol (D-BT), a precursor to the energetic material D-butanetriol trinitrate (D-BTTN), using our technology for engineering metabolic complexes in living cells. We have proposed the following specific aims: Specific Aim 1: Co-localization of D-BT enzymes into functional metabolic complexes. Under this aim, we will assemble the D-BT pathway enzymes into functional complexes using covalent and non-covalent methods of assembly/crosslinking developed here and in conjunction with studies under N000140610565. We will also explore the use of computational tools as a means to design protein-protein interactions de novo. Specific Aim 2: Enable combinatorial engineering of metabolic complexes via metabolite sensors. We will engineer a collection of protein-based switches that are capable of dynamically responding to our desired end-product D-BT over a broad concentration range. Such sensors will enable fine-tuning (e.g., laboratory evolution) of our engineered D-BT channels.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2008
- Accession Number
- ADA573196
Entities
People
- Matthew P. DeLisa
Organizations
- Cornell University