Heterologous Production of the C33–C45 Polyketide Fragment of Anticancer Apratoxins in a Cyanobacterial Host
Dipesh Dhakal, Dimitris Kallifidas, Man‐Yun Chen, Sofia Kokkaliari, Qi-Yin Chen, Valerie J. Paul, Yousong Ding, Hendrik Luesch
Abstract
A polyketide synthase subcluster of cytotoxic apratoxin A was isolated from a Moorena bouillonii environmental DNA library and engineered with a thioesterase II domain for heterologous expression in the filamentous cyanobacterium Anabaena sp. PCC7120. Further engineering with a rhamnose-inducible promoter led to the production of (2 R,3 R,5 R,7 R )-3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid, a stereogenically rich chiral building block that is important to the efficient synthesis of apratoxin analogues, representing the first synthetic biology attempt for this type of polyketide fragment.
Topics & Concepts
PolyketideHeterologousChemistryHeterologous expressionThioesteraseDNAPolyketide synthaseFragment (logic)BiochemistryBiosynthesisStereochemistryRecombinant DNAGeneComputer scienceProgramming languageMicrobial Natural Products and BiosynthesisMarine Sponges and Natural ProductsAlgal biology and biofuel production