Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

“…In addition, elucidating the stereochemistry of 4 also allowed us to assign the absolute configurations of 1 and 2 as 2 S ,3 S ,6 R ,10 R ,11 R , raising a possibility that 1 might be the biosynthetic precursor of roussoellol C, a cytotoxic FC-type diterpenoid isolated from T. purpurogenus PP-414 [ 7 ]. It will be important to elucidate the biosynthetic pathway of roussoellol C, providing enzymatic tools for expanding the chemical diversity of talaro-7,13-diene related FC-type diterpenoids via combinational biosynthesis [ 14 ].…”

“…Along with the development of low-cost sequencing technologies and tractable heterologous expression systems, genome mining has become a promising strategy for targeted discovery of natural products [10][11][12], which can also provide enzymatic tools toward combinatorial biosynthesis [13,14]. As terpene synthases play a fundamental role in constructing molecular skeletons, great efforts have been devoted to mining novel synthases in pursuit of new terpenoids [15][16][17].…”

Biosynthetic characterization of the antifungal fernane-type triterpenoid polytolypin for generation of new analogues via combinatorial biosynthesis

“…In addition, we have also established a stochastic combinational strategy, which is conducted through random assembly of tailoring enzymes from different biosynthetic pathways with the core enzymes for the common intermediate. 19 Therefore, it is expected that the chemical diversity of fernane-type triterpenoids can be extensively expanded by using these two strategies.…”

“…15 On the basis of systematically elucidating the biosynthetic pathways of fusidane-type antibiotics, 16–18 we have recently developed a stochastic combinational biosynthetic strategy based on random assembly of post-tailoring genes in a strain producing their common intermediate, which significantly expands the chemical diversity of fusidane-type antibiotics. 19…”

“…15 On the basis of systematically elucidating the biosynthetic pathways of fusidane-type antibiotics, [16][17][18] we have recently developed a stochastic combinational biosynthetic strategy based on random assembly of post-tailoring genes in a strain producing their common intermediate, which significantly expands the chemical diversity of fusidane-type antibiotics. 19 In this work, we have identified the biosynthetic gene cluster of polytolypin (1) from its producer Polytolypa hystricis UAMH7299 13 and characterized its biosynthetic pathway. A new fernane-type triterpene cyclase is responsible for the biosynthesis of motiol, which is subsequently oxidized by three cytochrome P450s to give polytolypin.…”