▁two ▁of ▁these ▁de h ydro am ino ▁acid ▁resid ues . ▁This ▁cycl ization ▁includes ▁a ▁D iels - A lder ▁type ▁reaction , ▁de h yd r ation , ▁and ▁elim ination ▁of ▁the ▁leader ▁pe pt ide . ▁An ▁ind ol ic ▁acid ▁mo iety ▁modified ▁from ▁L - try pt oph an ▁is ▁then ▁lig ated ▁to ▁the ▁un mod ified ▁c yst e ine ▁resid ue ▁through ▁a ▁th io ester ▁link age . ▁After ▁m eth yl ation ▁and ▁ox id ation ▁of ▁the ▁ind ole , ▁the ▁second ▁macro cycle ▁is ▁formed ▁by ▁reaction ▁of ▁the ▁ind ole ▁hydro x yl ▁group ▁with ▁the ▁free ▁car box yl ▁group ▁of ▁the ▁nearby ▁gl ut am ate ▁resid ue . ▁The ▁now ▁f used ▁b icy clic ▁pe pt ide ▁under go es ▁several ▁ox id ations ▁and ▁partial ▁cle av age ▁of ▁the ▁C - term inal ▁de h ydro al an ine ▁resid ue ▁to ▁give ▁the ▁m ature ▁nos ihe pt ide . ▁ ▁The ▁translation ▁and ▁modification ▁of ▁the ▁prec ursor ▁pe pt ide ▁is ▁undert aken ▁by ▁several ▁en zym es ▁encoded ▁in ▁a ▁local ized ▁gene ▁cluster ▁containing ▁ 1 4 ▁struct ural ▁gen es ▁and ▁ 1 ▁regul atory ▁gene . ▁One ▁of ▁these ▁gen es ▁enc odes ▁the ▁pe pt ide , ▁and ▁the ▁others ▁are ▁responsible ▁for ▁the ▁post trans l ational ▁modifications . ▁ ▁Total ▁synth esis ▁ ▁The ▁first ▁total ▁synth esis ▁was ▁published ▁by ▁Ar