Dedication: Heinz Floss and Christopher Walsh—pioneers in natural product chemical biology

In January 2018 the Society for Industrial Microbiology and Biotechnology (SIMB), the Korean Society for Microbiology and Biotechnology (KMB), and the Society for Actinomycetes Japan (SAJ) cosponsored the Natural Products Discovery and Development in the Genomic Era. This meeting, attended by researchers from across the globe, was dedicated to two pioneers in the field of natural products—Heinz Floss and Christopher Walsh. These investigators helped lay the foundation for natural product research as it progresses in the Genomic Era. Combined, they contributed to our understanding of the details of the biosynthesis of a significant number of antibiotics, anticancer agents, and many other microbial natural products. The fruits of the large body of work contributed by Floss and Walsh can be seen in their combination over 1300 publications that have served to define mechanistic natural product biosynthetic chemical biology over the past 4 decades, the number of successful companies, large and small, they have advised, and perhaps most importantly, the quantity and quality of researchers that have trained under their supervision who are their tangible legacy and continue to advance the field of natural product research. At the meeting, the outcomes of this foundational influence were in evidence. Currently, the field of natural products is experiencing a renaissance, neatly paralleling the historical renaissance of the 15th and 16th centuries that saw the rediscovery of classical art and science following a period of intellectual regression and stagnation rightly known as the Dark Ages. The advances of natural product chemistry and biology were profoundly felt in the mid-20th century with the development of analytical techniques for their purification and characterization along with an understanding of the basic principles of their biosynthesis using technologies such as stable isotope incorporation along with chemical and biochemical studies. However, it is the application of natural products on the development of drugs for humans and animals ranging from antibiotics and anticancer agents, to insecticides, nematicides, and immune suppressors that distinguishes this field from many others. Floss and Walsh contributed significantly to this era, but it is their work in the ‘natural product Dark Ages’—the 1980s to early 2000s—that has been revolutionary. These Dark Ages are defined by a pivot in industry and academia away from natural products in drug discovery toward high-throughput chemistry and screening of smaller, less complex chemical entities. This marginalized the impact of natural products on the development of new antibiotics and other drugs. At the same time, Floss, Walsh, and a select few others toiled to advance natural product research through the multidisciplinary application of new technologies in molecular biology and biochemistry, focused through the lens of rigorous chemical thinking. The results are nothing short of transformative, providing fundamental understanding of the logic of, for example, assembly-line biosynthesis of polyketides such as the ansamycins, and non-ribosomal peptides such as vancomycin. Their insights into linking the discovery of natural product biosynthetic gene clusters and the transformative chemistry required for the assembly of a final product * Gerard D. Wright wrightge@mcmaster.ca