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Metabolic Engineering Working Group

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  Panel Session


Notes on Panel Session: MEWG Workshop, 6 Feb 2004


Jay Keasling

Chaitan Khosla

Michael Betenbaugh

Jacqueline Shanks

Lonnie Ingram

Peter Karp

Moderator -- Mark Segal

Each panelist was asked to present a brief overview of the expected impacts of their work. In addition each panelist was to address, as a roundtable, specific questions concerning the direction ME is moving and how their work fits in, what societal issues can be addressed by ME, what common themes are addressed by ME research and what research emphasis should MEWG place in its next announcement of opportunities.

Michael Betenbaugh pointed out that ME addresses either improved yield of improved "quality" of metabolic products in mammalian systems. By quality, he indicated that he meant the synthesis of entirely new products from modified pathways that could not otherwise be generated through traditional genetic manipulations. He thought ME could address issues associated with the cell cycle, including timing of events, and address such issues as the cell death pathway, which is not usually included in the concept of ME. Jay Keasling thought that better use of "omics" could be employed, and that ME could be used to create new chemistries. Jackie Shanks believed that the goal of an in silico plant, much as has been done for other organisms, is a worthy one. However, ME needs to become predictive as well as evaluative, leading to iterative hypothesis testing. We need to model plants with secondary metabolic pathways more complex than Arabidopsis – medicinal plants are one such category. Shanks was interested in seeing support for quantitative proteomics, metabolite profiling and metabolic flux analysis in plants and other organisms. Theoretical frameworks and tools are needed for systems analysis of biological organisms. Peter Karp was interested in seeing genome sequences for every host of interest to ME in order to build a robust enough data set that could be used to systematically address the commonalities and differences of pathways. Therefore, using the annotations from the sequencing, he would like to see modeling of the metabolic network of these hosts. He especially wanted to see development of enzyme genomics, the assignment of sequences to all function, i. e. as defined by E.C. numbers. Lonnie Ingram echoed some of what the others said and suggested we need to use ME to develop entirely new products, taking advantage of our increasing knowledge of biological diversity. We need more ME effort directed and unusual organisms like extremeophiles. Chaitan Khosla also agreed with much of what went before and added that the MEWG needed to be sure that it catalyzed research in areas ignored by the usually funding mechanisms of the agencies involved with ME.

When asked for comments on the set of topics in the MEWG announcements of the past, several panelists agreed that the topics --- instrumentation, sensors, new analytical tools, and new experimental methods, which facilitate the study of metabolic pathways, especially those technologies that allow the examination of individual cells; quantitative and conceptual models integrated with experimental studies that better characterize the regulation and integration of complex, interacting metabolic pathways; and the use of bioinformatics to deduce the structure, function, and regulation of major metabolic pathways --- were not unique to metabolic engineering. There was agreement from the panel on the "tools" that should be developed to better address metabolic engineering problems. In that vein, Keasling’s call for better use of "omics" tools and Karp’s suggestion of characterizing the enzymes of hosts organisms sequenced and used used in ME are important examples of what the tools focus could look like. Many of the best proposals will probably combine both cutting edge tools as applied to particular problems. However, some proposals may be primarily tools-focused while the majority are likely to address specific problems related to particular needs of a specific agency.

Khosla and Betenbaugh stressed the need to have an explicit focus on engineering new metabolic pathways and a need to either identify entirely new problems in ME or to develop new innovative approaches to existing ones. As the panel noted, there are numerous important problems already being addressed from global warming (Ingram) to feeding the world’s population (Shanks) to health care in underdeveloped world (Khosla and Keasling) to heath care costs in the US (Betenbaugh). A suggestion from the audience to direct the topics of future announcements to specific societal needs was not well received. What was clear to the panel members was that the different mandates of the cooperating agencies and the likely impossibility of limiting any announcement to a particular need all could agree upon makes it very difficult to agree on specific societal problems to address. Individual researchers will only feel qualified to tackle specific problems.

Background on the Panel Session

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