Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458, USA.
J Am Chem Soc. 2013 Feb 20;135(7):2489-92. doi: 10.1021/ja4002635. Epub 2013 Feb 11.
The iso-migrastatin (iso-MGS) biosynthetic gene cluster from Streptomyces platensis NRRL 18993 consists of 11 genes, featuring an acyltransferase (AT)-less type I polyketide synthase (PKS) and three tailoring enzymes MgsIJK. Systematic inactivation of mgsIJK in S. platensis enabled us to (i) identify two nascent products of the iso-MGS AT-less type I PKS, establishing an unprecedented novel feature for AT-less type I PKSs, and (ii) account for the formation of all known post-PKS biosynthetic intermediates generated by the three tailoring enzymes MgsIJK, which possessed significant substrate promiscuities.
链霉菌 NRRL18993 中的异迁移他汀(iso-MGS)生物合成基因簇由 11 个基因组成,具有酰基转移酶(AT)缺失型 I 型聚酮合酶(PKS)和三个修饰酶 MgsIJK。系统敲除链霉菌中的 mgsIJK,使我们能够:(i)鉴定出异 MGS AT 缺失型 I 型 PKS 的两个新生产物,为 AT 缺失型 I 型 PKS 建立了一个前所未有的新特征;(ii)解释由三个修饰酶 MgsIJK 生成的所有已知的后 PKS 生物合成中间体的形成,这些酶具有显著的底物混杂性。