Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement

• DOI: 10.1039/c3sc52015c
• Publication Date: 2013-09-26T14:07:20Z
• Authors: Heng Guo; Jiang Wang; Yeming Li; Yi Yu; Qingfei Zheng; Jiequn Wu; Wen Liu
• Keywords: Thiostrepton; Residue (chemistry)

The ribosomal origin of thiopeptide antibiotics, a class sulfur-rich and highly modified poly(thi)azolyl natural products, has recently been uncovered features complex post-translational modifications (PTMs) precursor peptide. Based on molecular engineering production improvement, we report insight into the biosynthesis two bicyclic compounds, thiostrepton nosiheptide. PTMs tolerate variations in first amino acids core peptide part peptide: (1) mutation Ile1 to Val had no apparent effect maturation, suggesting that attachment quinaldic moiety at position 1 is not residue-dependent for construction side ring system; (2) change Ala2 Ser led exclusively an analog bears corresponding dehydroamino acid residue, indicating dehydration 2 site-selective or oxazoline formed by cyclodehydration inaccessible maturation. For nosiheptide particular, provide structural evidence specific system precedes formation common central heterocycle domain therefore propose characteristic framework interweaves both are interdependent. above efforts benefited from development uniform approach examine effectiveness trans expression gene encoding peptides associated PTM capacity. This independent knowledge regarding organism-specific regulatory mechanisms potentially applicable other systems produce ribosomally synthesized products.