Awakawa Takayoshi, Crüsemann Max, Munguia Jason, Ziemert Nadine, Nizet Victor, Fenical William, Moore Bradley S
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Chembiochem. 2015 Jul 6;16(10):1443-7. doi: 10.1002/cbic.201500177. Epub 2015 May 15.
Salinipyrones and pacificanones are structurally related polyketides from Salinispora pacifica CNS-237 that are proposed to arise from the same modular polyketide synthase (PKS) assembly line. Genome sequencing revealed a large macrolide PKS gene cluster that codes for the biosynthesis of rosamicin A and a series of new macrolide antibiotics. Mutagenesis experiments unexpectedly correlated salinipyrone and pacificanone biosynthesis to the rosamicin octamodule Spr PKS. Remarkably, this bifurcated polyketide pathway illuminates a series of enzymatic domain- and module-skipping reactions that give rise to natural polyketide product diversity. Our findings enlarge the growing knowledge of polyketide biochemistry and illuminate potential challenges in PKS bioengineering.
盐霉素和太平洋霉素是来自太平洋盐孢菌CNS-237的结构相关聚酮化合物，推测它们由同一条模块化聚酮合酶（PKS）装配线产生。基因组测序揭示了一个大型大环内酯PKS基因簇，该基因簇编码玫瑰霉素A和一系列新的大环内酯抗生素的生物合成。诱变实验意外地将盐霉素和太平洋霉素的生物合成与玫瑰霉素八模块Spr PKS联系起来。值得注意的是，这种分叉的聚酮途径揭示了一系列导致天然聚酮产物多样性的酶结构域和模块跳跃反应。我们的发现扩展了对聚酮生物化学不断增长的认识，并揭示了PKS生物工程中的潜在挑战。
