Discovery and biosynthetic pathway analysis of cyclopentane–β-lactone globilactone A

摘要: Naturally occurring β-lactone compounds are a class of strained four-membered heterocycles and can act as highly reactive electrophiles. Despite intensive studies for several decades, fewer than 30 β-lactones, many of which have high clinical potential, have been characterized from microorganisms. Here we report the discovery of a β-lactone compound, globilactone A through heterologous expression of a polyketide synthase/non-ribosomal peptide synthetase-like biosynthetic gene cluster (glo) in Streptomyces albus J1074. Biosynthetic pathway studies revealed that the polyketide synthase part can synthesize a polyunsaturated polyketide chain. While the downstream non-ribosomal peptide synthetase-like module, comprising condensation, FkbH, peptidyl carrier protein and thioester reductase domains (C–FkbH–PCP–R), incorporates a three-carbon pyruvate unit, and mediates formation of two carbon …