Nosiheptide is a prototypal thiopeptide antibiotic, containing an indole side ring in addition to its thiopeptide-characteristic macrocylic scaffold. This indole ring is derived from 3-methyl-2-indolic acid (MIA), a product of the radical S-adenosylmethionine enzyme NosL, but how MIA is incorporated into nosiheptide biosynthesis remains to be investigated. Here we report functional dissection of a series of enzymes involved in nosiheptide biosynthesis. We show NosI activates MIA and transfers it to the phosphopantetheinyl arm of a carrier protein NosJ. NosN then acts on the NosJ-bound MIA and installs a methyl group on the indole C4, and the resulting dimethylindolyl moiety is released from NosJ by a hydrolase-like enzyme NosK. Surface plasmon resonance analysis show that the molecular complex of NosJ with NosN is much more stable than those with other enzymes, revealing an elegant biosynthetic strategy in which the reaction flux is controlled by protein–protein interactions with different binding affinities.

The catalytic reactions proceed with good yields with a low catalyst loading (1 mol%) under aerobic and CuI-free conditions for Sonogashira and Heck reactions.

An efficient and practical method for the one-pot Mannich reaction of aromatic ketones with aldehydes and amines at room temperature has been developed under solvent-free conditions catalyzed by (C 4 H 12 N 2) 2 [BiCl 6 ]Cl•H 2 O (3 mol%). The catalyst may also be recycled multiple times by simple isolation protocols without compromising the catalytic efficiency.

Tyrosine analogues containing an olefin moiety can be adenosylated by l-tyrosine lyases.

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