As John Archibald Wheeler said, "We live on an island of knowledge surrounded by a sea of ignorance. As our island of knowledge grows, so does the shore of our ignorance." So as the B3 conference added to our collective store of knowledge, it also helped point out more of our areas of ignorance. As we ponder the future, an important question to ask is the following: How broad is natural biocatalysis? This question is also important in the broader context of genomic biology, whereby genome annotators seek to match up sequences with functions. Since most microbial genes encode enzymes that catalyze reactions, we desperately need to know whether or not we are knowledgeable about most of the reaction types catalyzed by microbes. The answer to this question has important implications for genome annotation and biotechnological advancement. There are some indicators suggesting that, regarding reaction types, our shore of ignorance is large. A significant proportion of the B3 conference was concerned with the action of oxygenases, which are critically important in aerobic biodegradation and for commercial biotransformations. However, we are still ignorant about the metabolism of several dozen chemical functional groups found in biologically produced compounds (94). This is despite the fact that many new reactions have been discovered recently; for example, biological equivalents of the following named organic reactions have been discovered: the Diels-Alder reaction, the Bamberger rearrangement, the Beckman rearrangement, and the Kolbe-Schmidt reaction. The B3 conference discussed novel biocatalysis and new ways of using well-known enzymes, but clearly more novel metabolism will be discovered before the next B3 conference convenes. Such discovery will increase the toolkit of enzymes that are usable in biotechnology. The expanded toolkit will provide new routes to synthesize a broad array of commodity chemicals from renewable resources. The use of renewable resources for clean and sustainable industry is clearly one of the major outcomes of B3.
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