Staunton J, Caffrey P, Aparicio J F, Roberts G A, Bethell S S, Leadlay P F
University Chemical Laboratory, University of Cambridge, UK.
Nat Struct Biol. 1996 Feb;3(2):188-92. doi: 10.1038/nsb0296-188.
Modular polyketide synthases are multienzymes responsible for the biosynthesis of a large number of clinically important natural products. They contain multiple sets, or modules, of enzymatic activities, distributed between a few giant multienzymes and there is one module for every successive cycle of polyketide chain extension. We show here that each multienzyme in a typical modular polyketide synthase forms a (possibly helical) parallel dimer, and that each pair of identical modules interacts closely across the dimer interface. Such an arrangement would allow identical modules to share active sites for chain extension, and thus to function independently of flanking modules, which would have important implications both for mechanisms of evolution of polyketide synthases and for their future genetic engineering.
模块聚酮合酶是负责大量具有临床重要性的天然产物生物合成的多酶。它们含有多组或多个模块的酶活性，分布在少数几个巨大的多酶之间，并且聚酮链延伸的每个连续循环都有一个模块。我们在此表明，典型模块聚酮合酶中的每个多酶形成一个（可能是螺旋状的）平行二聚体，并且每对相同的模块在二聚体界面处紧密相互作用。这样的排列将允许相同的模块共享用于链延伸的活性位点，从而独立于侧翼模块发挥作用，这对于聚酮合酶的进化机制及其未来的基因工程都将具有重要意义。
