Bertin Matthew J, Vulpanovici Alexandra, Monroe Emily A, Korobeynikov Anton, Sherman David H, Gerwick Lena, Gerwick William H
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, MC 0212, La Jolla, CA, 92093, USA.
Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences, 2750 SW Campus Way, Corvallis, OR, 97331, USA.
Chembiochem. 2016 Jan;17(2):164-73. doi: 10.1002/cbic.201500467. Epub 2015 Dec 23.
Phormidolide is a polyketide produced by a cultured filamentous marine cyanobacterium and incorporates a 16-membered macrolactone. Its complex structure is recognizably derived from a polyketide synthase pathway, but possesses unique and intriguing structural features that prompted interest in investigating its biosynthetic origin. Stable isotope incorporation experiments confirmed the polyketide nature of this compound. We further characterized the phormidolide gene cluster (phm) through genome sequencing followed by bioinformatic analysis. Two discrete trans-type acyltransferase (trans-AT) ORFs along with KS-AT adaptor regions (ATd) within the polyketide synthase (PKS) megasynthases, suggest that the phormidolide gene cluster is a trans-AT PKS. Insights gained from analysis of the mode of acetate incorporation and ensuing keto reduction prompted our reevaluation of the stereochemistry of phormidolide hydroxy groups located along the linear polyketide chain.
甲藻内酯是一种由培养的丝状海洋蓝细菌产生的聚酮化合物，含有一个16元大环内酯。其复杂结构明显源自聚酮合酶途径，但具有独特且引人入胜的结构特征，这引发了人们对研究其生物合成起源的兴趣。稳定同位素掺入实验证实了该化合物的聚酮性质。我们通过基因组测序和生物信息学分析进一步对甲藻内酯基因簇（phm）进行了表征。聚酮合酶（PKS）大型合酶内的两个离散的反式型酰基转移酶（trans-AT）开放阅读框以及KS-AT衔接区（ATd），表明甲藻内酯基因簇是一种反式-AT PKS。对乙酸掺入模式和随后的酮还原分析所获得的见解促使我们重新评估沿着线性聚酮链的甲藻内酯羟基的立体化学。
