Figure 1.

Natural product biosynthetic gene clusters. (a) Representation of the diversity of size and complexity of NPs and their encoding gene clusters, including tyrvalin, a pyrazinone virulence factor from skin-associated staphylococci²¹⁰, platensimycin, a diterpenoid antibiotic from soil-dwelling Streptomyces isolates²¹¹, pederin, a polyketide anticancer agent produced by an uncultivated symbiont of the Paederus spp. beetles²¹, and bryostatin, a macrocyclic lactone anticancer agent produced by a symbiont of a marine bryozoan²¹². Approximate sizes of BGCs for select NPs (black), along with noteworthy examples of large systems that have been built with synthetic DNA technology in wild type (red) or re-designed (green) genetic architecture. (b) Widening gap of uncharacterized PKS enzymes (grey) compared to biochemically characterized PKSs (black) since 2000 (data to 2010 reproduced from Wong and Khosla²¹³; 2014 data point from Marnix Medema, personal communication). Dashed line represents best fit to available data points. (c) Recent history of DNA synthesis costs²¹⁴ and the corresponding number of 50 kb gene clusters that could be synthesized with $100k. Dotted lines project to the future along the same trajectory of the past 15 years.