CHAPTER 15

Biosynthesis

15.1 Overview of Biosynthesis

15.2 CO2 Fixation: The Calvin Cycle

15.3 CO2 Fixation: Diverse Pathways

15.4 Biosynthesis of Fatty Acids and Polyketides

15.5 Nitrogen Fixation and Regulation

15.6 Biosynthesis of Amino Acids and Nitrogenous Bases

How do microbes build their cells? Some bacteria and archaea build themselves entirely from carbon dioxide and nitrogen gas, plus a few salts. The cell assimilates carbon and nitrogen into small molecules and then assembles more complex structures using many enzymes. How do cells organize their biosynthesis to build precisely the forms they need? How do bacteria avoid wasting energy on excess production? New genomes reveal new microbial capacities for biosynthesis, ranging from antibiotics and pesticides to surgical materials.

In Chapters 13 and 14 we learned how microbes use chemical reactions to gain energy, storing it in ion gradients and in small molecules such as ATP and NADPH. Chapter 15 shows how the microbes spend this energy for biosynthesis. An example is Amycolatopsis MJM2582, the actinomycete bacterium isolated by South Korean biochemist Hee-Jeon Hong and colleagues at the University of Cambridge, including her student Min Jun Kwun (Fig. 15.1). The white fuzz on the actinomycete colonies is full of arthrospores (see Chapters 5 and 18), which can blow off to another location. When the cell filaments enter stationary phase (discussed in Chapter 4), they begin to produce dozens of different secondary products, such as the antibiotic ristocetin (Fig. 15.1, inset). Such antibiotics show extraordinary diversity and complexity, often including multiple aromatic rings—a surprising biosynthetic feat for an organism that’s running out of resources. But the antibiotics enable the producer to outcompete other bacteria, killing them to scavenge their substrates for biosynthesis. Antibiotic synthesis requires elaborate enzyme complexes and multistep reaction pathways. Hong’s lab identified such a pathway in the Amycolatopsis genome. The genome reveals a span of 79,000 base pairs comprising thirty-nine genes for enzymes, regulators, and transporters—all to produce and export the antibiotic ristocetin.

FIGURE 15.1 Discovering a new antibiotic-producing actinomycete. A. Min Jung Kwun discovered the actinomycete Amycolatopsis MJM2582. B. Amycolatopsis MJM2582 cultured for 7 days at 30°C on mannitol soya agar, a medium that encourages sporulation (white fuzz). The actinomycete produces ristocetin (inset), a glycopeptide antibiotic.

Chapter 15 presents the fundamental ways that microbes perform biosynthesis. Autotrophs assimilate elements such as carbon and nitrogen to build useful carbon skeletons, key functions in the food web. Microbial enzyme factories build remarkably complex biomolecules, including vitamins and antibiotics important for human health. Industrial applications of microbial biosynthesis are described in Chapter 16.