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B6db references: 31882449

type Journal Article
authors Dai GZ, Han WB, Mei YN, Xu K, Jiao RH, Ge HM, Tan RX
title Pyridoxal-5'-phosphate-dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi
journal Proc Natl Acad Sci U S A.
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year (2020)
volume 117
number 2
pages 1174-1180
keywords doi: 10.1073/pnas.1914777117
abstract Indolizidine alkaloids are widespread in nature, diverse in structure, prominent in bioactivity, and elusive in ecology, but only a few have been biosynthetically clarified. Here, we describe the biosynthesis of curvulamine, a unique antibacterial indolizidine alkaloid from Curvularia sp. IFB-Z10. Unexpectedly, curvulamine results from a consortium of 6 enzymes including a pyridoxal-5′-phosphate (PLP)-dependent bifunctional aminotransferase (CuaB) catalyzing the formation of C−C (via Claisen condensation) and C−O bonds (using dioxygen). Guided by the CuaB function, our genome mining effort revealed, from a single silent gene cluster, a collection of previously undescribed polyketide alkaloids with 1 more antibacterial than curvulamine. Collectively, the work describes an unprecedented construction of indolizidine-coined skeletons and provides another layer of the functional versatility to the PLP-dependent enzymes.
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