Identification cloning and heterologous expression of the abyssomicin C biosynthetic gene cluster

抗菌药物耐药性在英国和国外都是一个日益严重的问题;多重耐药微生物是医院和社区获得性感染的原因，仅在英国每年估计就花费10亿英镑。在过去的几十年里，通过过度使用和滥用临床抗生素，已经产生了耐药性。这个问题已经恶化，由于新的抗微生物化合物还没有从制药行业即将到来的事实;可能是由于研究议程的变化。为了保持领先多药耐药微生物一步，需要新的抗菌剂;临床上重要的微生物不会暴露于这些化合物，因此尚未获得耐药性。最近，从日本海的微生物分离物中鉴定出一种新的抗菌剂，即Abyssomicin C，该化合物被证明能有效杀死包括MRSA在内的多重耐药微生物。为了充分发挥这种化合物的潜力，我们希望进行旨在发现这种海洋生物如何制造深海菌素C的研究。一旦我们了解了这种化合物是如何产生的，我们就可以改进生产（以便为未来的临床研究提供足够的材料），确定用于生产新的新型化合物的新化学，并确定其他可能产生类似化合物的生物体，这些化合物对多药耐药微生物具有不同的活性。我们希望这项研究将有助于提供新的抗菌化合物，供未来在临床上使用，有助于防止日益严重的微生物耐药性问题。

Antimicrobial drug resistance is a growing problem both in the UK and abroad; multi-drug resistant microbes are responsible for hospital- and community- acquired infections and are estimated to cost £1 billion per year in the UK alone. Drug-resistance has developed through the over-use and misuse of clinical antibiotics for the past few decades. This problem has been worsened due to the fact that new antimicrobial compounds have not been forthcoming from the pharmaceutical industry; likely due to a change in research agendas. In order to keep one-step ahead of multi-drug resistant microbes, new antimicrobial are required; clinically significant microbes will not have been exposed to these compounds and so will have not yet acquired resistance. Recently, a novel antimicrobial, abyssomicin C, was identified from a microbe isolate from the Sea of Japan, this compound was shown to be effective at killing multi-drug resistant microbes, including MRSA. In order, to fully realize the potential of this compound, we wish to undertake research aimed at discovering how this marine organism makes abyssomicin C. Once we understand how this compound is made, we can improve production (in order to provide enough material for future clinical research), identify novel chemistry for the production of new novel compounds, and identify other organisms that may produce similar compounds with different activities against multi-drug resistant microbes. We hope that this research will help to provide new antimicrobial compounds for future use in the clinic, helping to prevent the growing problem of microbial drug resistance.