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In contrast to the classical notion that enzymes always carry out highly specific reaction towards particular substrate,recent studies highlight both the widespread and underestimated biological functions of promiscuous enzymes,referred to those with cross-reactivity.However,the impact of such enzyme clusters on the performance of microbial cell factories was rarely explored up to now.Inspired by this scope,we hypothesized the general existence of interaction between target biosynthesis pathway and host metabolic network introduced by the endogenous promiscuous enzymes and set out to characterize its potential impact on metabolic engineering.